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(A) Western blot analysis of histone methylation (H3K4me1 and H3K4me4) in SEM and Lin− MLL-Af4 cells, control or depleted for IGF2BP3; n = 3. (B) Dot blot analysis of m 6 A modification (left) and methylene blue staining in SEM cells, control or depleted for IGF2BP3. (C) ELISA measurement of m 6 A modification on RNA isolated from SEM, Lin− MLL-Af4, and NALM6 cells ( n = 4 for SEM and Lin− MLL-Af4, n = 5 [sg5 = 3] for NALM6). (D) Bar plot (left) and pie chart (right) depicting the m 6 A peak distribution across genomic locations from the m 6 A-eCLIP data in SEM control and IGF2BP3-depleted cells. (E) Metagene plots depicting the changes in the m 6 A peak coverage across the transcriptome in SEM control and IGF2BP3-depleted cells. (F) Volcano plot (top) for genes showing differential m 6 A RNA methylation after IGF2BP3 depletion and IGF2BP3 targets defined by eCLIP analysis. Gray dashed lines indicate the significant cutoffs for differential expression (±1) and the adjusted p value (0.05). Hypomethylated genes are highlighted in blue, while hypermethylated genes are highlighted in red. IGV browser snapshots (bottom) of m 6 A-eCLIP depicting the coverage and change in the peak height between the NT and IGF2BP3-depleted cells for <t>MAT2A</t> 3′ UTR are shown. All data are n ≥ 3 replicates represented as mean ± standard deviation (SD), compared by two-sided unpaired t test; * p < 0.05, ** p < 0.01, and *** p < 0.001. In case of missing or outlier values, the replicate was not reported. All experiments were repeated at least twice for consistency. All the western blots were repeated at least three times to report the changes, if any. Refer also to .

Mat2a, supplied by Proteintech, used in various techniques. Bioz Stars score: 93/100, based on 26 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Average 93 stars, based on 26 article reviews

mat2a - by Bioz Stars, 2026-03

93/100 stars

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1) Product Images from "IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation"

Article Title: IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation

Journal: Cell reports

doi: 10.1016/j.celrep.2025.116330

Figure Legend Snippet: (A) Western blot analysis of histone methylation (H3K4me1 and H3K4me4) in SEM and Lin− MLL-Af4 cells, control or depleted for IGF2BP3; n = 3. (B) Dot blot analysis of m 6 A modification (left) and methylene blue staining in SEM cells, control or depleted for IGF2BP3. (C) ELISA measurement of m 6 A modification on RNA isolated from SEM, Lin− MLL-Af4, and NALM6 cells ( n = 4 for SEM and Lin− MLL-Af4, n = 5 [sg5 = 3] for NALM6). (D) Bar plot (left) and pie chart (right) depicting the m 6 A peak distribution across genomic locations from the m 6 A-eCLIP data in SEM control and IGF2BP3-depleted cells. (E) Metagene plots depicting the changes in the m 6 A peak coverage across the transcriptome in SEM control and IGF2BP3-depleted cells. (F) Volcano plot (top) for genes showing differential m 6 A RNA methylation after IGF2BP3 depletion and IGF2BP3 targets defined by eCLIP analysis. Gray dashed lines indicate the significant cutoffs for differential expression (±1) and the adjusted p value (0.05). Hypomethylated genes are highlighted in blue, while hypermethylated genes are highlighted in red. IGV browser snapshots (bottom) of m 6 A-eCLIP depicting the coverage and change in the peak height between the NT and IGF2BP3-depleted cells for MAT2A 3′ UTR are shown. All data are n ≥ 3 replicates represented as mean ± standard deviation (SD), compared by two-sided unpaired t test; * p < 0.05, ** p < 0.01, and *** p < 0.001. In case of missing or outlier values, the replicate was not reported. All experiments were repeated at least twice for consistency. All the western blots were repeated at least three times to report the changes, if any. Refer also to .

Techniques Used: Western Blot, Methylation, Control, Dot Blot, Modification, Staining, Enzyme-linked Immunosorbent Assay, Isolation, Quantitative Proteomics, Standard Deviation

(A) Western blot analysis of Lin− cells from Igf2bp3 del/del mice. Briefly, cells were isolated from mice with a germline deletion of Igf2bp3, transformed with MLL-Af4, and then subjected to transduction with MSCV-based constructs carrying the wild-type murine Igf2bp3. Proteins that were analyzed are Igf2bp3, Mat2a, Mat2b, and actin. (B) Cell growth, measured by CellTiter-Glo, over 4 days in Igf2bp3 del/del Lin− MLL-Af4 cells with enforced IGF2BP3 expression as above. Viability has been normalized to control cells; mean ± standard deviation (SD) ( n = 5); one-way ANOVA followed by Bonferroni’s multiple comparisons test; **** p < 0.0001. (C) Representative Seahorse XF extracellular acidification rate (ECAR) kinetic trace in cells described above ( n = 4). (D) Aggregate lactate efflux rates from Seahorse XF analysis in cells described above; two-sided unpaired t test; * p < 0.05 ( n = 4). (E) Colony formation assays from Lin− MLL-Af4 cells as described above; two-sided unpaired t test; ** p < 0.01 ( n = 2). (F) ELISA measurement of m 6 A modification on RNA isolated from Igf2bp3 del/del Lin− MLL-Af4 cells with enforced IGF2BP3 expression as above; two-sided unpaired t test; * p < 0.05 ( n = 3). (G) Percentage engraftment of CD45.2 Lin− cells in bone marrow from Igf2bp3 del/del mice transduced with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (H) Quantitation of bone marrow count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (I) Spleen weights of mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (J) Quantitation of spleen cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (K) Quantitation of bone marrow CD11b+ cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (L) Quantitation of bone marrow Lin− cell count along with representative fluorescence-activated cell sorting (FACS) plots in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (M) Quantitation of bone marrow CD11b+cKit+ cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (N) Quantitation of bone marrow LSK (Lin− cKit+Sca1−) cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (O) Quantitation of bone marrow CD11b+Sca1− (potential LIC ) cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (P) Seahorse XF ECAR kinetic trace for bone marrow cells isolated from the empty vector (Ctrl) or IGF2BP3 re-expression group at 6 weeks ( n = 4, each group; for representation n = 2). (Q) Aggregate lactate efflux rates from Seahorse XF analysis in cells described above; reported as mean ± SD ( n = 4). (R) ELISA measurement of m 6 A RNA modifications in splenic tumors isolated from mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks; reported as mean ± SD; 8 mice/group. (S) H&E staining of spleen of mice transplanted with mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. Scale bar: 100 μm. (T) Overall survival of mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups (representative graph cumulative of two experiments, 8 mice/group; the experiment was terminated after 12 weeks; Kaplan-Meier method with log rank test was used to report the results). The animal experiments were repeated twice. All the western blots were repeated at least three times to report the changes, if any. Data in this figure are represented as mean ± SD with n = 8 mice per group. Statistical tests were performed using two-sided unpaired t test with significance levels as indicated; * p < 0.05, ** p < 0.01, and *** p < 0.001. Refer also to and .

Figure Legend Snippet: (A) Western blot analysis of Lin− cells from Igf2bp3 del/del mice. Briefly, cells were isolated from mice with a germline deletion of Igf2bp3, transformed with MLL-Af4, and then subjected to transduction with MSCV-based constructs carrying the wild-type murine Igf2bp3. Proteins that were analyzed are Igf2bp3, Mat2a, Mat2b, and actin. (B) Cell growth, measured by CellTiter-Glo, over 4 days in Igf2bp3 del/del Lin− MLL-Af4 cells with enforced IGF2BP3 expression as above. Viability has been normalized to control cells; mean ± standard deviation (SD) ( n = 5); one-way ANOVA followed by Bonferroni’s multiple comparisons test; **** p < 0.0001. (C) Representative Seahorse XF extracellular acidification rate (ECAR) kinetic trace in cells described above ( n = 4). (D) Aggregate lactate efflux rates from Seahorse XF analysis in cells described above; two-sided unpaired t test; * p < 0.05 ( n = 4). (E) Colony formation assays from Lin− MLL-Af4 cells as described above; two-sided unpaired t test; ** p < 0.01 ( n = 2). (F) ELISA measurement of m 6 A modification on RNA isolated from Igf2bp3 del/del Lin− MLL-Af4 cells with enforced IGF2BP3 expression as above; two-sided unpaired t test; * p < 0.05 ( n = 3). (G) Percentage engraftment of CD45.2 Lin− cells in bone marrow from Igf2bp3 del/del mice transduced with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (H) Quantitation of bone marrow count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (I) Spleen weights of mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (J) Quantitation of spleen cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (K) Quantitation of bone marrow CD11b+ cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (L) Quantitation of bone marrow Lin− cell count along with representative fluorescence-activated cell sorting (FACS) plots in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (M) Quantitation of bone marrow CD11b+cKit+ cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (N) Quantitation of bone marrow LSK (Lin− cKit+Sca1−) cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (O) Quantitation of bone marrow CD11b+Sca1− (potential LIC ) cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (P) Seahorse XF ECAR kinetic trace for bone marrow cells isolated from the empty vector (Ctrl) or IGF2BP3 re-expression group at 6 weeks ( n = 4, each group; for representation n = 2). (Q) Aggregate lactate efflux rates from Seahorse XF analysis in cells described above; reported as mean ± SD ( n = 4). (R) ELISA measurement of m 6 A RNA modifications in splenic tumors isolated from mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks; reported as mean ± SD; 8 mice/group. (S) H&E staining of spleen of mice transplanted with mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. Scale bar: 100 μm. (T) Overall survival of mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups (representative graph cumulative of two experiments, 8 mice/group; the experiment was terminated after 12 weeks; Kaplan-Meier method with log rank test was used to report the results). The animal experiments were repeated twice. All the western blots were repeated at least three times to report the changes, if any. Data in this figure are represented as mean ± SD with n = 8 mice per group. Statistical tests were performed using two-sided unpaired t test with significance levels as indicated; * p < 0.05, ** p < 0.01, and *** p < 0.001. Refer also to and .

Techniques Used: Western Blot, Isolation, Transformation Assay, Transduction, Construct, Expressing, Control, Standard Deviation, Enzyme-linked Immunosorbent Assay, Modification, Plasmid Preparation, Quantitation Assay, Cell Counting, Fluorescence, FACS, Staining

Image Search Results

A Score plot depicting the separation of metabolic gene patterns in the human DW and NDW groups through PCA analysis in GSE154556 . B Volcano plot showing the differentially expressed metabolic genes between human DWs and NDWs in GSE154556 . Differentially expressed genes were assessed with the limma moderated two-sided t test. C KEGG analysis of typical differential metabolic pathways between human DWs and NDWs in GSE154556 . D t-SNE plots of the characterized cell clusters identified via scRNA-seq of human wound samples ( GSE165816 ). E Venn diagram showing the shared altered metabolic differential genes and their origins. F Correlation analysis of the expression levels of the metabolic candidates and the inflammatory macrophage infiltration score in GSE154556 . The text annotations above showed the cellular origins of the main differences of these candidates analyzed from GSE165816 . G Cellular communication analysis revealing potential interactions among pericytes with low MAT2A expression and other cell types from GSE165816 . H Schematic illustration of the methionine cycle, and the relative levels of methionine in the human DW and NDW groups. n = 12 biologically independent samples. I Expression levels of metabolic enzymes involved in the methionine cycle in the two groups ( GSE165816 ). Non-parametric two-sided Wilcoxon rank-sum test was used. J Immunofluorescence staining and statistical analysis demonstrating the expression levels of MAT2A in CD31-NG2+PDGFRβ+ pericytes from human wounds. n = 3 biologically independent samples. K Pericytes were classified into samples with high MAT2A expression levels and samples with low MAT2A expression levels ( GSE165816 ); grouped samples were analyzed via GSEA. The median expression of the gene was used as the dividing line. Data were shown as mean ± SD. Statistical significance was determined using hypergeometric test ( C ) and two-tailed unpaired t test ( H , J ). Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: A Score plot depicting the separation of metabolic gene patterns in the human DW and NDW groups through PCA analysis in GSE154556 . B Volcano plot showing the differentially expressed metabolic genes between human DWs and NDWs in GSE154556 . Differentially expressed genes were assessed with the limma moderated two-sided t test. C KEGG analysis of typical differential metabolic pathways between human DWs and NDWs in GSE154556 . D t-SNE plots of the characterized cell clusters identified via scRNA-seq of human wound samples ( GSE165816 ). E Venn diagram showing the shared altered metabolic differential genes and their origins. F Correlation analysis of the expression levels of the metabolic candidates and the inflammatory macrophage infiltration score in GSE154556 . The text annotations above showed the cellular origins of the main differences of these candidates analyzed from GSE165816 . G Cellular communication analysis revealing potential interactions among pericytes with low MAT2A expression and other cell types from GSE165816 . H Schematic illustration of the methionine cycle, and the relative levels of methionine in the human DW and NDW groups. n = 12 biologically independent samples. I Expression levels of metabolic enzymes involved in the methionine cycle in the two groups ( GSE165816 ). Non-parametric two-sided Wilcoxon rank-sum test was used. J Immunofluorescence staining and statistical analysis demonstrating the expression levels of MAT2A in CD31-NG2+PDGFRβ+ pericytes from human wounds. n = 3 biologically independent samples. K Pericytes were classified into samples with high MAT2A expression levels and samples with low MAT2A expression levels ( GSE165816 ); grouped samples were analyzed via GSEA. The median expression of the gene was used as the dividing line. Data were shown as mean ± SD. Statistical significance was determined using hypergeometric test ( C ) and two-tailed unpaired t test ( H , J ). Source data are provided as a Source Data file.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Expressing, Immunofluorescence, Staining, Two Tailed Test

A ScRNA-seq profiling workflow created with BioRender.com. B Western blot analysis of MAT2A expression in pericytes isolated from the indicated mouse skin. C Representative images of cutaneous wounds of mice on days 0, 4, 8, 12, and 16 after wound model generation by surgical excision. Ratio of wound sizes were quantified by using ImageJ software and were calculated by the percentages of wound closure compared to day 0 wound size. n = 3 mice for sampling at the indicated time points. D Representative blood perfusion images and statistical analysis of wounds at days 4 and 8 after surgery. E Cutaneous wound sections were subjected to H&E and Masson’s trichrome staining, and IHC staining for Ki-67, α-SMA, and IL6 were performed. Samples were collected at day 8 after wound model generation. n = 3 mice for sampling at the indicated time points. Scale bar, 100 μm. F UMAP plot showing identified cell clusters of mouse skin. G Representative immunofluorescence images and statistical analysis demonstrating the pericyte abundance in cutaneous wounds on day 4. H Volcano plot showing the differential genes of pericyte clusters between the two groups based on P value < 0.05 and absolute log 2 (Fold Change) > 0.25. Non-parametric two-sided Wilcoxon rank-sum test was used. I Bar graph showing the functionally enriched pathways associated with the significantly upregulated or downregulated genes (MAT2A LOF vs. control) in the pericyte clusters. J Cellular communication analysis revealing potential interactions among pericytes and other cell types. K Violin-box plots representing the expression of proinflammatory or anti-inflammatory signature genes in the macrophage clusters. Macrophage cells in control group, n = 6201; macrophage cells in MAT2A LOF group, n = 6763. L UMAP plot and quantitative analysis showing characterized cell clusters of infiltrated macrophages and their proportions in the indicated groups. M Cell trajectory analysis of the characterized cell clusters of infiltrated macrophages. N Representative immunofluorescence images and statistical analysis demonstrating the macrophageinfiltration in cutaneous wound tissues on day 8. n = 3 mice in each group. Scale bar, 20 μm. For the box and violin-box plots in ( G ), and ( K ), the centerlines indicated the medians. The box limits indicated the first and third quartiles. The whiskers indicated the maxima and minima. Data in the bar plots were shown as mean ± SD. n = 3 biologically independent samples ( D , G ). Statistical significance was determined using two-way ANOVA with Tukey’s multiple comparisons test ( C ) and two-tailed unpaired t test ( D , G , K , N ). Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: A ScRNA-seq profiling workflow created with BioRender.com. B Western blot analysis of MAT2A expression in pericytes isolated from the indicated mouse skin. C Representative images of cutaneous wounds of mice on days 0, 4, 8, 12, and 16 after wound model generation by surgical excision. Ratio of wound sizes were quantified by using ImageJ software and were calculated by the percentages of wound closure compared to day 0 wound size. n = 3 mice for sampling at the indicated time points. D Representative blood perfusion images and statistical analysis of wounds at days 4 and 8 after surgery. E Cutaneous wound sections were subjected to H&E and Masson’s trichrome staining, and IHC staining for Ki-67, α-SMA, and IL6 were performed. Samples were collected at day 8 after wound model generation. n = 3 mice for sampling at the indicated time points. Scale bar, 100 μm. F UMAP plot showing identified cell clusters of mouse skin. G Representative immunofluorescence images and statistical analysis demonstrating the pericyte abundance in cutaneous wounds on day 4. H Volcano plot showing the differential genes of pericyte clusters between the two groups based on P value < 0.05 and absolute log 2 (Fold Change) > 0.25. Non-parametric two-sided Wilcoxon rank-sum test was used. I Bar graph showing the functionally enriched pathways associated with the significantly upregulated or downregulated genes (MAT2A LOF vs. control) in the pericyte clusters. J Cellular communication analysis revealing potential interactions among pericytes and other cell types. K Violin-box plots representing the expression of proinflammatory or anti-inflammatory signature genes in the macrophage clusters. Macrophage cells in control group, n = 6201; macrophage cells in MAT2A LOF group, n = 6763. L UMAP plot and quantitative analysis showing characterized cell clusters of infiltrated macrophages and their proportions in the indicated groups. M Cell trajectory analysis of the characterized cell clusters of infiltrated macrophages. N Representative immunofluorescence images and statistical analysis demonstrating the macrophageinfiltration in cutaneous wound tissues on day 8. n = 3 mice in each group. Scale bar, 20 μm. For the box and violin-box plots in ( G ), and ( K ), the centerlines indicated the medians. The box limits indicated the first and third quartiles. The whiskers indicated the maxima and minima. Data in the bar plots were shown as mean ± SD. n = 3 biologically independent samples ( D , G ). Statistical significance was determined using two-way ANOVA with Tukey’s multiple comparisons test ( C ) and two-tailed unpaired t test ( D , G , K , N ). Source data are provided as a Source Data file.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Western Blot, Expressing, Isolation, Software, Sampling, Staining, Immunohistochemistry, Immunofluorescence, Control, Two Tailed Test

A Gene set enrichment analysis derived from the single-cell transcriptome profiling of the wound margin tissue showing the differential biological processes in the pericyte clusters between MAT2A LOF group and control group. NES, Nominal Enrichment Score. FDR P values were calculated based on the one-tailed test on the appropriate side of the null distribution. B Gene set variation analysis derived from the single-cell transcriptome profiling showing the significant enrichment of senescence-related pathway terms in the pericyte clusters. C Box plot showing the recommendation indices of six SIDs for the pericyte cluster ( n = 2211 cells), with SID3 presenting the highest values. D Box plot showing the SID3 scores of pericyte clusters between the MAT2A LOF ( n = 1025 cells) and control groups ( n = 1186 cells). E UMAP plots showing the distribution of SID3 scores of pericyte clusters in the indicated groups. F Immunostaining and statistical analysis of P21 (Red) and NG2 (Green) in cutaneous wound tissues between the control group and the MAT2A LOF group. Scale bar, 20 μm. G Effect of Mat2a knockdown on pericyte senescence, as determined by SAHF formation (H3K9me3 staining) and SA-β-gal staining. Pericytes were isolated from the mouse skins. H Western blot analysis determining the expression levels of P21 and Lamin B1 of pericytes in the indicated groups. I , J OCR measurement and maximal respiration analysis of pericytes with or without Mat2a knockdown. K Bar plot showing the cellular ATP levels of pericytes with or without Mat2a knockdown. L Bar plots showing MAT2A mRNA levels in cells from humans and mice. For the box plots in ( C ), and ( D ), the centerlines indicated the medians. The box limits indicated the first and third quartiles. The whiskers indicated the maxima and minima. Data in the bar plots were shown as mean ± SD. n = 3 biologically independent samples ( F , G , I , J , K ). Statistical significance was determined using one-way ANOVA with Tukey’s multiple comparisons test ( G ) and two-tailed unpaired t test ( D , F , J , K ). Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: A Gene set enrichment analysis derived from the single-cell transcriptome profiling of the wound margin tissue showing the differential biological processes in the pericyte clusters between MAT2A LOF group and control group. NES, Nominal Enrichment Score. FDR P values were calculated based on the one-tailed test on the appropriate side of the null distribution. B Gene set variation analysis derived from the single-cell transcriptome profiling showing the significant enrichment of senescence-related pathway terms in the pericyte clusters. C Box plot showing the recommendation indices of six SIDs for the pericyte cluster ( n = 2211 cells), with SID3 presenting the highest values. D Box plot showing the SID3 scores of pericyte clusters between the MAT2A LOF ( n = 1025 cells) and control groups ( n = 1186 cells). E UMAP plots showing the distribution of SID3 scores of pericyte clusters in the indicated groups. F Immunostaining and statistical analysis of P21 (Red) and NG2 (Green) in cutaneous wound tissues between the control group and the MAT2A LOF group. Scale bar, 20 μm. G Effect of Mat2a knockdown on pericyte senescence, as determined by SAHF formation (H3K9me3 staining) and SA-β-gal staining. Pericytes were isolated from the mouse skins. H Western blot analysis determining the expression levels of P21 and Lamin B1 of pericytes in the indicated groups. I , J OCR measurement and maximal respiration analysis of pericytes with or without Mat2a knockdown. K Bar plot showing the cellular ATP levels of pericytes with or without Mat2a knockdown. L Bar plots showing MAT2A mRNA levels in cells from humans and mice. For the box plots in ( C ), and ( D ), the centerlines indicated the medians. The box limits indicated the first and third quartiles. The whiskers indicated the maxima and minima. Data in the bar plots were shown as mean ± SD. n = 3 biologically independent samples ( F , G , I , J , K ). Statistical significance was determined using one-way ANOVA with Tukey’s multiple comparisons test ( G ) and two-tailed unpaired t test ( D , F , J , K ). Source data are provided as a Source Data file.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Derivative Assay, Single Cell, Control, One-tailed Test, Immunostaining, Knockdown, Staining, Isolation, Western Blot, Expressing, Two Tailed Test

$A Bubble map showing the interactions of selected ligand-receptor pairs between pericytes and macrophage subsets. The communication strengths of interacting molecule 1 in cluster 1 and interacting molecule 2 in cluster 2 were indicated by color gradients (blue, low level; red, high level). The P values were calculated with the CellChat one-sided permutation test and indicated by the circle size. B Top panel: The coculture workflow of pericytes with or without Mat2a knockdown and macrophages (bone marrow-derived macrophages). Bottom panel: RT-qPCR analysis of inflammatory signature genes in macrophages. In the contact coculture system, the macrophages were collected through magnetic bead cell sorting (MACS). The workflow was created with BioRender.com. C Heatmap representing the change direction of senescence associated secretion phenotype in pericytes within the wound margin of the indicated groups. D In vitro RT-qPCR verifying the expression of a subset of typical SASP factors in pericytes with or without Mat2a knockdown. E Bar plots showing the Rcm values across a wide range of rank cutoffs (10%-100%) for pericytes within the wound margin of the MAT2A LOF group and the control group. The labels A1-A3 and B1-B3 represent the sample numbers within the groups. F Violin plots depicting the estimated strength (left) and fraction (right) of macrophage-derived mitochondria in pericytes predicted by MERCI between the MAT2A LOF group (n = 154 cells) and control group (n = 184 cells). G In vitro coculture of GFP+ pericytes and mitoDsRed+ macrophages immunostained with β-actin (white) to visualize the membrane boundaries of the two cell types, emphasized with high magnification. Arrows indicate transferred mitoDsRed+ mitochondria in pericytes. Scale bar, 10 μm.For the violin-box plots in ( F ), the centerlines indicated the medians. The box limits indicated the first and third quartiles. The whiskers indicated the maxima and minima. Data in the bar plots were shown as mean ± SD. n = 3 biologically independent samples ( B , D , G ). Statistical significance was determined using one-way ANOVA with Tukey’s multiple comparisons test ( D ) and two-tailed unpaired t test ( B , F , G ). Source data are provided as a Source Data file.$

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: A Bubble map showing the interactions of selected ligand-receptor pairs between pericytes and macrophage subsets. The communication strengths of interacting molecule 1 in cluster 1 and interacting molecule 2 in cluster 2 were indicated by color gradients (blue, low level; red, high level). The P values were calculated with the CellChat one-sided permutation test and indicated by the circle size. B Top panel: The coculture workflow of pericytes with or without Mat2a knockdown and macrophages (bone marrow-derived macrophages). Bottom panel: RT-qPCR analysis of inflammatory signature genes in macrophages. In the contact coculture system, the macrophages were collected through magnetic bead cell sorting (MACS). The workflow was created with BioRender.com. C Heatmap representing the change direction of senescence associated secretion phenotype in pericytes within the wound margin of the indicated groups. D In vitro RT-qPCR verifying the expression of a subset of typical SASP factors in pericytes with or without Mat2a knockdown. E Bar plots showing the Rcm values across a wide range of rank cutoffs (10%-100%) for pericytes within the wound margin of the MAT2A LOF group and the control group. The labels A1-A3 and B1-B3 represent the sample numbers within the groups. F Violin plots depicting the estimated strength (left) and fraction (right) of macrophage-derived mitochondria in pericytes predicted by MERCI between the MAT2A LOF group (n = 154 cells) and control group (n = 184 cells). G In vitro coculture of GFP+ pericytes and mitoDsRed+ macrophages immunostained with β-actin (white) to visualize the membrane boundaries of the two cell types, emphasized with high magnification. Arrows indicate transferred mitoDsRed+ mitochondria in pericytes. Scale bar, 10 μm.For the violin-box plots in ( F ), the centerlines indicated the medians. The box limits indicated the first and third quartiles. The whiskers indicated the maxima and minima. Data in the bar plots were shown as mean ± SD. n = 3 biologically independent samples ( B , D , G ). Statistical significance was determined using one-way ANOVA with Tukey’s multiple comparisons test ( D ) and two-tailed unpaired t test ( B , F , G ). Source data are provided as a Source Data file.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Knockdown, Derivative Assay, Quantitative RT-PCR, FACS, In Vitro, Expressing, Control, Membrane, Two Tailed Test

A Effect of endogenous Mat2a knockdown followed by restoration of Mat2a WT, MUT1 or SAM (500 μM) on pericyte senescence, as determined by SAHF formation (H3K9me3 staining) and SA-β-gal staining ( n = 3). B Western blot assessment of the expression levels of P21 and Lamin B1 in the indicated pericytes. C – E OCR measurement, maximal respiration analysis and cellular ATP assessment of pericytes following endogenous Mat2a knockdown with Mat2a WT, MUT1 or SAM (500 μM) restoration ( n = 3). F Scheme displaying the procedure used for identifying the specific targets of MAT2A through proteomic and IP-MS analysis. The workflow was created with BioRender.com. G Heatmap showing the change direction of differential proteins in pericytes with or without Mat2a knockdown. H Display showed the differentially regulated proteins, categorized per known or predicted function(s), literature and sequence similarity. Circle size was proportional to the number of differentially expressed proteins. I Intersection of the results from the proteomics and IP-MS analyses. J Scheme displaying the HMGCS1-mediated MVA pathway. K IP and WB analyses showing the interaction of MAT2A and HMGCS1 in 293T cells with indicated transfections. L In vitro binding analysis of MAT2A and HMGCS1 with GST pull-down assays. M Design of MAT2A and HMGCS1 truncations. N IP and WB analysis representing the interactions between Flag-tagged truncated MAT2A and His-tagged PRMT1 proteins in 293T cells. O IP and WB analysis representing the interactions between His-tagged truncated HMGCS1 and Flag-tagged MAT2A proteins in 293T cells. P Molecular docking showing the interaction between MAT2A truncation (slate) and HMGCS1 truncation (cyan). Q Docked positions of MAT2A and HMGCS1 and design of the mutations of binding sites between MAT2A and HMGCS1. R IP and WB analysis of the interactions between FLAG-tagged MAT2A mutation (MUT2) and His-tagged HMGCS1 mutation in 293T cells. Data were shown as mean ± SD. n = 3 biologically independent samples ( A , C , D , E ). Statistical significance was determined using one-way ANOVA with Tukey’s multiple comparisons test ( A , D , E ). n.s. no significance. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: A Effect of endogenous Mat2a knockdown followed by restoration of Mat2a WT, MUT1 or SAM (500 μM) on pericyte senescence, as determined by SAHF formation (H3K9me3 staining) and SA-β-gal staining ( n = 3). B Western blot assessment of the expression levels of P21 and Lamin B1 in the indicated pericytes. C – E OCR measurement, maximal respiration analysis and cellular ATP assessment of pericytes following endogenous Mat2a knockdown with Mat2a WT, MUT1 or SAM (500 μM) restoration ( n = 3). F Scheme displaying the procedure used for identifying the specific targets of MAT2A through proteomic and IP-MS analysis. The workflow was created with BioRender.com. G Heatmap showing the change direction of differential proteins in pericytes with or without Mat2a knockdown. H Display showed the differentially regulated proteins, categorized per known or predicted function(s), literature and sequence similarity. Circle size was proportional to the number of differentially expressed proteins. I Intersection of the results from the proteomics and IP-MS analyses. J Scheme displaying the HMGCS1-mediated MVA pathway. K IP and WB analyses showing the interaction of MAT2A and HMGCS1 in 293T cells with indicated transfections. L In vitro binding analysis of MAT2A and HMGCS1 with GST pull-down assays. M Design of MAT2A and HMGCS1 truncations. N IP and WB analysis representing the interactions between Flag-tagged truncated MAT2A and His-tagged PRMT1 proteins in 293T cells. O IP and WB analysis representing the interactions between His-tagged truncated HMGCS1 and Flag-tagged MAT2A proteins in 293T cells. P Molecular docking showing the interaction between MAT2A truncation (slate) and HMGCS1 truncation (cyan). Q Docked positions of MAT2A and HMGCS1 and design of the mutations of binding sites between MAT2A and HMGCS1. R IP and WB analysis of the interactions between FLAG-tagged MAT2A mutation (MUT2) and His-tagged HMGCS1 mutation in 293T cells. Data were shown as mean ± SD. n = 3 biologically independent samples ( A , C , D , E ). Statistical significance was determined using one-way ANOVA with Tukey’s multiple comparisons test ( A , D , E ). n.s. no significance. Source data are provided as a Source Data file.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Knockdown, Staining, Western Blot, Expressing, Protein-Protein interactions, Sequencing, Transfection, In Vitro, Binding Assay, Mutagenesis

A HMGCS1 expression levels in pericytes with Mat2a knockdown followed by transfection of Mat2a WT or MUT2. B HMGCS1 expression levels in pericytes treated with cycloheximide (CHX, 100 μg/ml) for the indicated times (top) and relative HMGCS1 protein levels (bottom). C HMGCS1 expression levels in Mat2a -knockdown pericytes treated with or without 10 μM MG132 for 8 h. D Ubiquitination of HMGCS1 in pericytes with the indicated transfections and treatment with 10 μM MG132 for 8 h. E Identification of ubiquitination related modification factors from IP/MS data. HMGCS1 expression levels in pericytes following Otub1 knockdown with or without WT restoration. The workflow was created with BioRender.com. F Ubiquitination of HMGCS1 in 293T cells with transfection of OTUB1 or the indicated mutant and treatment with 10 μM MG132 for 8 h. G Co-localization analysis of MAT2A, OTUB1 and HMGCS1 by immunofluorescence staining in pericytes. H Binding analysis of HMGCS1 and OTUB1 following MAT2A transfection or not in 293T cells treated with 10 μM MG132 for 8 h. I Ubiquitination of HMGCS1 in 293T cells with the indicated transfection of OTUB1 and MAT2A and treatment with 10 μM MG132 for 8 h. J Binding analysis of HMGCS1 and OTUB1 following MAT2A knockdown or not in 293T cells treated with 10 μM MG132 for 8 h. K Ubiquitination of HMGCS1 in 293T cells with the indicated transfection of OTUB1 and knockdown of MAT2A and treatment with 10 μM MG132 for 8 h. L Co-localization analysis of OTUB1 and HMGCS1 following Mat2a knockdown by immunofluorescence staining in pericytes. Data were shown as mean ± SD. n = 3 biologically independent samples ( B ). Statistical significance was determined using two-way ANOVA with Tukey’s multiple comparisons test ( B ). n.s. no significance. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: A HMGCS1 expression levels in pericytes with Mat2a knockdown followed by transfection of Mat2a WT or MUT2. B HMGCS1 expression levels in pericytes treated with cycloheximide (CHX, 100 μg/ml) for the indicated times (top) and relative HMGCS1 protein levels (bottom). C HMGCS1 expression levels in Mat2a -knockdown pericytes treated with or without 10 μM MG132 for 8 h. D Ubiquitination of HMGCS1 in pericytes with the indicated transfections and treatment with 10 μM MG132 for 8 h. E Identification of ubiquitination related modification factors from IP/MS data. HMGCS1 expression levels in pericytes following Otub1 knockdown with or without WT restoration. The workflow was created with BioRender.com. F Ubiquitination of HMGCS1 in 293T cells with transfection of OTUB1 or the indicated mutant and treatment with 10 μM MG132 for 8 h. G Co-localization analysis of MAT2A, OTUB1 and HMGCS1 by immunofluorescence staining in pericytes. H Binding analysis of HMGCS1 and OTUB1 following MAT2A transfection or not in 293T cells treated with 10 μM MG132 for 8 h. I Ubiquitination of HMGCS1 in 293T cells with the indicated transfection of OTUB1 and MAT2A and treatment with 10 μM MG132 for 8 h. J Binding analysis of HMGCS1 and OTUB1 following MAT2A knockdown or not in 293T cells treated with 10 μM MG132 for 8 h. K Ubiquitination of HMGCS1 in 293T cells with the indicated transfection of OTUB1 and knockdown of MAT2A and treatment with 10 μM MG132 for 8 h. L Co-localization analysis of OTUB1 and HMGCS1 following Mat2a knockdown by immunofluorescence staining in pericytes. Data were shown as mean ± SD. n = 3 biologically independent samples ( B ). Statistical significance was determined using two-way ANOVA with Tukey’s multiple comparisons test ( B ). n.s. no significance. Source data are provided as a Source Data file.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Expressing, Knockdown, Transfection, Ubiquitin Proteomics, Modification, Protein-Protein interactions, Mutagenesis, Immunofluorescence, Staining, Binding Assay

A Cellular CoQ levels in pericytes with Mat2a knockdown. B MAT2A and HMGCS1 expression levels in pericytes with the indicated transfections. C Cellular CoQ levels in pericytes with Mat2a knockdown followed by transfection of Mat2a MUT2, Hmgcs1 , or not. D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration. E , F ATP assessment and cell viability in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ restoration. G SA-β-gal staining in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ restoration. H Expression levels of P21 and Lamin B1 in pericytes subjected to the indicated treatments. I RT-qPCR analysis showing the expression levels of typical SASP components in pericytes subjected to the indicated treatments. J , K MitoDsRed+ macrophages were co-cultured with GFP+ pericytes following the indicated treatment. GFP+ MitoDsRed+ pericytes were quantified via flow cytometry ( J ), as summarized in ( K ).Data were shown as mean ± SD. n = 3 biologically independent samples ( A , C – G , I , K ). Statistical significance was determined using two-tailed unpaired t test ( A ), one-way ANOVA with Tukey’s multiple comparisons test ( C – E , G , I , K ) and two-way ANOVA with Tukey’s multiple comparisons test ( F ). n.s. no significance. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: A Cellular CoQ levels in pericytes with Mat2a knockdown. B MAT2A and HMGCS1 expression levels in pericytes with the indicated transfections. C Cellular CoQ levels in pericytes with Mat2a knockdown followed by transfection of Mat2a MUT2, Hmgcs1 , or not. D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration. E , F ATP assessment and cell viability in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ restoration. G SA-β-gal staining in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ restoration. H Expression levels of P21 and Lamin B1 in pericytes subjected to the indicated treatments. I RT-qPCR analysis showing the expression levels of typical SASP components in pericytes subjected to the indicated treatments. J , K MitoDsRed+ macrophages were co-cultured with GFP+ pericytes following the indicated treatment. GFP+ MitoDsRed+ pericytes were quantified via flow cytometry ( J ), as summarized in ( K ).Data were shown as mean ± SD. n = 3 biologically independent samples ( A , C – G , I , K ). Statistical significance was determined using two-tailed unpaired t test ( A ), one-way ANOVA with Tukey’s multiple comparisons test ( C – E , G , I , K ) and two-way ANOVA with Tukey’s multiple comparisons test ( F ). n.s. no significance. Source data are provided as a Source Data file.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Knockdown, Expressing, Transfection, Staining, Quantitative RT-PCR, Cell Culture, Flow Cytometry, Two Tailed Test

Harmonious cellular communication and cooperation, as well as efficient transformation of cell phenotypes, are indispensable for wound regeneration. MAT2A downregulation mediated pericyte senescence in a moonlighting manner, which induced the infiltration of inflammatory macrophages in diabetic wounds. This discovery provides an saRNA-based strategy targeting senescent pericytes for wound healing. The diagram was created with BioRender.com.

Journal: Nature Communications

Article Title: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models

doi: 10.1038/s41467-025-65659-2

Figure Lengend Snippet: Harmonious cellular communication and cooperation, as well as efficient transformation of cell phenotypes, are indispensable for wound regeneration. MAT2A downregulation mediated pericyte senescence in a moonlighting manner, which induced the infiltration of inflammatory macrophages in diabetic wounds. This discovery provides an saRNA-based strategy targeting senescent pericytes for wound healing. The diagram was created with BioRender.com.

Article Snippet: D OCR measurement in pericytes with Mat2a knockdown followed by transfection of Hmgcs1 , or CoQ (TargetMol, USA, T2796) restoration.

Techniques: Transformation Assay

A The enrollment of TCFA-positive patients defined by OCT and schematic representation of the patients screened in the discovery cohort. This figure was created using images from PowerPoint and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/dmkgnf0 . B Partial least-squares discrimination analysis (PLS-DA) 3D score plots. C Volcano plot of significantly differential metabolites in monocytes. D Detection of monocytes methionine metabolism concentrations ( n = 38 subjects). E The final FCT was determined by averaging three measurements performed at the thinnest part of the fibrous cap. F Vulnerable plaque characteristics between patients with high and low SAM/SAH levels ( n = 38 subjects). G Multivariate logistic regression analysis revealing the relationship between high SAM/SAH levels and TCFA ( n = 76 for total subjects). H Representative OCT images of a normal coronary artery, a vulnerable plaque, and a stable plaque. Scale bar = 5 mm. I Schematic of the methionine metabolism pathway. J The mRNA levels in monocytes isolated from TCFA-positive and TCFA-negative individuals ( n = 38 subjects). UMAP visualization ( K ) and MAT2A expression ( L ) of human atherosclerotic carotid artery cells ( n = 15 patients, GSE253903 ). UMAP visualization ( M ) and MAT2A expression ( N ) of human atherosclerotic carotid artery myeloid cells. Representative immunofluorescence images ( O ) and quantification ( P ) of MAT2A and CD11b in carotid plaques from symptomatic and asymptomatic patients ( n = 6 subjects. Scale bar = 50 µm). C Two-tailed P-values were indicated. D The bar bands defined as 25th and 75th percentiles; the plot top line as median; two-tailed Mann–Whitney P -values are indicated. F The box shows the 25th, 50th and 75th percentiles of the data. The whiskers represent minimum and the maximum; Chi-squared test and two-tailed Mann–Whitney P -values was used. G The error bars represent the 95% CI for the OR, with their centers (red squares) indicating the point estimates; two-tailed P -values are shown. ( J , P ) Data are presented as the mean ± SD; two-tailed P -values are shown. L , N Log normalized using the ‘NormalizeData’ function in Seurat with default parameters. CKD chronic kidney disease, FCT fibrous cap thickness, MAT2A methionine adenosyltransferase Ⅱ alpha, OCT optical coherence tomography, SAH, S-adenosyl-homocysteine, SAM S-adenosyl-methionine, TCFA thin-cap fibroatheroma, UMAP uniform manifold approximation and projection. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages

doi: 10.1038/s41467-025-66121-z

Figure Lengend Snippet: A The enrollment of TCFA-positive patients defined by OCT and schematic representation of the patients screened in the discovery cohort. This figure was created using images from PowerPoint and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/dmkgnf0 . B Partial least-squares discrimination analysis (PLS-DA) 3D score plots. C Volcano plot of significantly differential metabolites in monocytes. D Detection of monocytes methionine metabolism concentrations ( n = 38 subjects). E The final FCT was determined by averaging three measurements performed at the thinnest part of the fibrous cap. F Vulnerable plaque characteristics between patients with high and low SAM/SAH levels ( n = 38 subjects). G Multivariate logistic regression analysis revealing the relationship between high SAM/SAH levels and TCFA ( n = 76 for total subjects). H Representative OCT images of a normal coronary artery, a vulnerable plaque, and a stable plaque. Scale bar = 5 mm. I Schematic of the methionine metabolism pathway. J The mRNA levels in monocytes isolated from TCFA-positive and TCFA-negative individuals ( n = 38 subjects). UMAP visualization ( K ) and MAT2A expression ( L ) of human atherosclerotic carotid artery cells ( n = 15 patients, GSE253903 ). UMAP visualization ( M ) and MAT2A expression ( N ) of human atherosclerotic carotid artery myeloid cells. Representative immunofluorescence images ( O ) and quantification ( P ) of MAT2A and CD11b in carotid plaques from symptomatic and asymptomatic patients ( n = 6 subjects. Scale bar = 50 µm). C Two-tailed P-values were indicated. D The bar bands defined as 25th and 75th percentiles; the plot top line as median; two-tailed Mann–Whitney P -values are indicated. F The box shows the 25th, 50th and 75th percentiles of the data. The whiskers represent minimum and the maximum; Chi-squared test and two-tailed Mann–Whitney P -values was used. G The error bars represent the 95% CI for the OR, with their centers (red squares) indicating the point estimates; two-tailed P -values are shown. ( J , P ) Data are presented as the mean ± SD; two-tailed P -values are shown. L , N Log normalized using the ‘NormalizeData’ function in Seurat with default parameters. CKD chronic kidney disease, FCT fibrous cap thickness, MAT2A methionine adenosyltransferase Ⅱ alpha, OCT optical coherence tomography, SAH, S-adenosyl-homocysteine, SAM S-adenosyl-methionine, TCFA thin-cap fibroatheroma, UMAP uniform manifold approximation and projection. Source data are provided as a Source Data file.

Article Snippet: To establish a pharmacological MAT2A inhibition model , , ApoE -/- mice were administered the MAT2A inhibitor FIDAS-5 (10 mg/kg, HY-136144, MedChemExpress, New Jersey, USA) by intragastric gavage.

Techniques: Isolation, Expressing, Immunofluorescence, Two Tailed Test, MANN-WHITNEY, Tomography

Both groups of 8-week-old female and male MAT2A fl/fl ApoE -/- and MAT2A CKO ApoE -/- mice were fed an HFD for 16 weeks. A Schematic figure showing the experimental strategy for the HFD feeding and the subsequent analysis. This figure was created using images from Photoshop and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/3iunh0m . B SAM and SAH concentrations as well as SAM/SAH ratio for mice monocyte cell lysate mass spectrometry samples ( n = 6). C Representative photographs of atherosclerotic plaques in the aortic arches and their branches in the 2 groups ( n = 10 mice per genotype). Representative images and quantification of Oil Red O-stained aortas ( D , n = 10 samples. Scale bar = 2 mm) and aortic roots ( E , n = 10 independent experiments. Scale bar = 200 µm). F , H , E and Masson’s trichrome staining of representative aortic root sections. Scale bar = 200 µm. G Quantification of plaque area, necrotic core, and collagen ( n = 10 samples). H and I , Immunohistochemistry of CD68 + macrophages and vulnerability index in the aortic roots ( n = 10 samples). Scale bar = 100 µm. Data are presented as the mean ± SD and comparisons were made using unpaired Student’s t -test; the two-tailed P -values are shown. α-SMA α-smooth muscle actin, HFD high-fat diet. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages

doi: 10.1038/s41467-025-66121-z

Figure Lengend Snippet: Both groups of 8-week-old female and male MAT2A fl/fl ApoE -/- and MAT2A CKO ApoE -/- mice were fed an HFD for 16 weeks. A Schematic figure showing the experimental strategy for the HFD feeding and the subsequent analysis. This figure was created using images from Photoshop and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/3iunh0m . B SAM and SAH concentrations as well as SAM/SAH ratio for mice monocyte cell lysate mass spectrometry samples ( n = 6). C Representative photographs of atherosclerotic plaques in the aortic arches and their branches in the 2 groups ( n = 10 mice per genotype). Representative images and quantification of Oil Red O-stained aortas ( D , n = 10 samples. Scale bar = 2 mm) and aortic roots ( E , n = 10 independent experiments. Scale bar = 200 µm). F , H , E and Masson’s trichrome staining of representative aortic root sections. Scale bar = 200 µm. G Quantification of plaque area, necrotic core, and collagen ( n = 10 samples). H and I , Immunohistochemistry of CD68 + macrophages and vulnerability index in the aortic roots ( n = 10 samples). Scale bar = 100 µm. Data are presented as the mean ± SD and comparisons were made using unpaired Student’s t -test; the two-tailed P -values are shown. α-SMA α-smooth muscle actin, HFD high-fat diet. Source data are provided as a Source Data file.

Techniques: Mass Spectrometry, Staining, Immunohistochemistry, Two Tailed Test

A Bubble chart of GO term enrichment analysis of downregulated DEGs based on RNA-seq in BMDMs of MAT2A CKO compared with MAT2A fl/fl mice. Flow cytometry was performed to quantify CD45 + CD11b + CD115 + Ly6C hi monocytes from bone marrow or peripheral blood ( B , n = 6 independent experiments), MHC Ⅱ and CCR2 ( C , n = 6 samples) on CD45 + CD68 + macrophages from aortic plaques of MAT2A CKO ApoE -/- and MAT2A fl/fl ApoE -/- mice fed a 16-week HFD. D – J Analysis of BMDMs from MAT2A CKO and MAT2A fl/fl mice treated with or without SAM (200 µM) following LPS and IFN-γ stimulation. Representative flow cytometry plots and quantification of CD45 + CD11b + CD86 + macrophages ( D , n = 6 samples), transwell ( E , n = 6 samples, Scale bar = 100 µm), and wound assay ( F , n = 6 samples. Scale bar = 500 µm). The mRNA levels of Il1b , Il6 , Nos2 ( G , n = 6 samples) and Ccl2 , Ccl7 and Cxcl1 ( H , n = 6 samples) measured by qRT-PCR. I , J The THP-1 cells were transfected with siNC or siMAT2A followed by LPS and IFN-γ treatment with or without SAM (200 µM). The mRNA levels of Il1b , Il6 , Nos2, Ccl2 , Ccl7 and Cxcl1 were analyzed by qRT-PCR ( n = 6 samples). A P -values were derived from hypergeometric distribution. Data are presented as the mean ± SD. B , C Unpaired Student’s t -test was used; two-tailed P values are shown. D – J One-way ANOVA was used; the adjusted P -values are shown. 8-week-old female and male mice were both used. BL blood, BM bone marrow, BMDMs bone marrow-derived macrophages, DEGs differentially expressed genes, GO gene ontology, IFN-γ interferon-γ, LPS lipopolysaccharide. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages

doi: 10.1038/s41467-025-66121-z

Figure Lengend Snippet: A Bubble chart of GO term enrichment analysis of downregulated DEGs based on RNA-seq in BMDMs of MAT2A CKO compared with MAT2A fl/fl mice. Flow cytometry was performed to quantify CD45 + CD11b + CD115 + Ly6C hi monocytes from bone marrow or peripheral blood ( B , n = 6 independent experiments), MHC Ⅱ and CCR2 ( C , n = 6 samples) on CD45 + CD68 + macrophages from aortic plaques of MAT2A CKO ApoE -/- and MAT2A fl/fl ApoE -/- mice fed a 16-week HFD. D – J Analysis of BMDMs from MAT2A CKO and MAT2A fl/fl mice treated with or without SAM (200 µM) following LPS and IFN-γ stimulation. Representative flow cytometry plots and quantification of CD45 + CD11b + CD86 + macrophages ( D , n = 6 samples), transwell ( E , n = 6 samples, Scale bar = 100 µm), and wound assay ( F , n = 6 samples. Scale bar = 500 µm). The mRNA levels of Il1b , Il6 , Nos2 ( G , n = 6 samples) and Ccl2 , Ccl7 and Cxcl1 ( H , n = 6 samples) measured by qRT-PCR. I , J The THP-1 cells were transfected with siNC or siMAT2A followed by LPS and IFN-γ treatment with or without SAM (200 µM). The mRNA levels of Il1b , Il6 , Nos2, Ccl2 , Ccl7 and Cxcl1 were analyzed by qRT-PCR ( n = 6 samples). A P -values were derived from hypergeometric distribution. Data are presented as the mean ± SD. B , C Unpaired Student’s t -test was used; two-tailed P values are shown. D – J One-way ANOVA was used; the adjusted P -values are shown. 8-week-old female and male mice were both used. BL blood, BM bone marrow, BMDMs bone marrow-derived macrophages, DEGs differentially expressed genes, GO gene ontology, IFN-γ interferon-γ, LPS lipopolysaccharide. Source data are provided as a Source Data file.

Techniques: RNA Sequencing, Flow Cytometry, Quantitative RT-PCR, Transfection, Derivative Assay, Two Tailed Test

A Immunoblots of H3K4me3, H3K36me3, and H3K27me3 levels in BMDMs from MAT2A fl/fl and MAT2A CKO mice ( n = 3). B Representative immunofluorescence images and quantification for H3K4me3 and CD68 in aortic root plaque from MAT2A fl/fl ApoE -/- and MAT2A CKO ApoE -/- mice fed a 16-week HFD ( n = 7). Scale bar = 100 µm. C – G Analysis of BMDMs between MAT2A CKO and MAT2A fl/fl mice. C Heatmaps for H3K4me3 binding peaks in BMDMs from MAT2A fl/fl and MAT2A CKO mice. D Venn diagram reflecting overlapping downregulated genes with H3K4me3 modification combining the CUT&Tag and RNA-seq data. Bubble charts of GO ( E ) and KEGG ( F ) analysis according to downregulated genes with decreased H3K4me3 modification. G IGV tracks revealing the results of CUT&Tag reads (H3K4me3 binding) distributions in indicated genes. H , I Analysis of BMDMs between MAT2A CKO and MAT2A fl/fl mice treated with or without SAM (200 µM) in the presence of LPS and IFN-γ. H ChIP-qPCR validation of H3K4me3 enrichment on the promoter regions of Aim2 , Ccl2 , and Mmp9 ( n = 6 samples). I ELISA analysis of AIM2, CCL2, and MMP9 in cellular supernatant ( n = 6 independent experiments). Data are presented as the mean ± SD. A , B Unpaired Student’s t -test was used; two-tailed P values are shown. E P -values were derived from hypergeometric distribution. H and I One-way ANOVA was used; the adjusted P -values are shown. Both 8-week-old female and male mice were used. ChIP-qPCR chromatin immunoprecipitation-qPCR, H3K4me3 histone h3 lysine 4 trimethylation, H3K27me3 histone H3 lysine 27 trimethylation, H3K36me3 histone h3 lysine 36 trimethylation, KEGG kyoto encyclopedia of genes and genomes, TSS translation start site. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages

doi: 10.1038/s41467-025-66121-z

Figure Lengend Snippet: A Immunoblots of H3K4me3, H3K36me3, and H3K27me3 levels in BMDMs from MAT2A fl/fl and MAT2A CKO mice ( n = 3). B Representative immunofluorescence images and quantification for H3K4me3 and CD68 in aortic root plaque from MAT2A fl/fl ApoE -/- and MAT2A CKO ApoE -/- mice fed a 16-week HFD ( n = 7). Scale bar = 100 µm. C – G Analysis of BMDMs between MAT2A CKO and MAT2A fl/fl mice. C Heatmaps for H3K4me3 binding peaks in BMDMs from MAT2A fl/fl and MAT2A CKO mice. D Venn diagram reflecting overlapping downregulated genes with H3K4me3 modification combining the CUT&Tag and RNA-seq data. Bubble charts of GO ( E ) and KEGG ( F ) analysis according to downregulated genes with decreased H3K4me3 modification. G IGV tracks revealing the results of CUT&Tag reads (H3K4me3 binding) distributions in indicated genes. H , I Analysis of BMDMs between MAT2A CKO and MAT2A fl/fl mice treated with or without SAM (200 µM) in the presence of LPS and IFN-γ. H ChIP-qPCR validation of H3K4me3 enrichment on the promoter regions of Aim2 , Ccl2 , and Mmp9 ( n = 6 samples). I ELISA analysis of AIM2, CCL2, and MMP9 in cellular supernatant ( n = 6 independent experiments). Data are presented as the mean ± SD. A , B Unpaired Student’s t -test was used; two-tailed P values are shown. E P -values were derived from hypergeometric distribution. H and I One-way ANOVA was used; the adjusted P -values are shown. Both 8-week-old female and male mice were used. ChIP-qPCR chromatin immunoprecipitation-qPCR, H3K4me3 histone h3 lysine 4 trimethylation, H3K27me3 histone H3 lysine 27 trimethylation, H3K36me3 histone h3 lysine 36 trimethylation, KEGG kyoto encyclopedia of genes and genomes, TSS translation start site. Source data are provided as a Source Data file.

Techniques: Western Blot, Immunofluorescence, Binding Assay, Modification, RNA Sequencing, ChIP-qPCR, Biomarker Discovery, Enzyme-linked Immunosorbent Assay, Two Tailed Test, Derivative Assay, Chromatin Immunoprecipitation

A – I The HFD-fed ApoE -/- mice were received either FIDAS-5 or vehicle every other day for 6 weeks. A, Flowchart illustrating the experimental procedure. This figure was created using images from Photoshop and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/h76jjnw . B Representative photographs of atherosclerotic plaques in the aortic arches and their branches. Representative images and quantification of Oil Red O-stained aortas ( C , n = 8. Scale bar = 2 mm) and aortic roots ( D and E , n = 8. Scale bar = 200 µm). F Representative images of H&E and Masson’s trichrome-stained aortic roots. Scale bar = 200 µm. G Quantification of plaque area, percentage of necrotic core, and collagen of aortic roots ( n = 8 per group). H , I Immunohistochemistry of CD68 + macrophages and vulnerability index in the aortic root plaque of FIDAS-5 treated mice, n = 8 per group. Scale bar = 100 µm. J – R Representative images of female and male mice fed MRD or CD for 6 weeks after a 10-week HFD. J Schematic figure showing the experimental strategy and subsequent analysis. This figure was created using images from Photoshop and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/h76jjnw . K Representative images of aortic arches and their branches in the indicated group. Representative images and quantification of Oil Red O-stained aortas ( L , n = 8. Scale bar = 2 mm) and aortic roots ( M and N , n = 8. Scale bar = 200 µm). O Representative images of H&E and Masson’s trichrome-stained aortic root. P Quantification of plaque area, percentage of necrotic core, and collagen, n = 8. Scale bar = 200 µm. Q and R Immunohistochemical staining CD68 + macrophages and vulnerability index, n = 8. Scale bar = 100 µm. Data are presented as mean ± SD and comparisons were made using unpaired Student’s t -test; two-tailed P values are shown. 8-week-old female and male ApoE -/- mice were used. FIDAS-5, a MAT2A inhibitor; MRD, methionine-restricted diet. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages

doi: 10.1038/s41467-025-66121-z

Figure Lengend Snippet: A – I The HFD-fed ApoE -/- mice were received either FIDAS-5 or vehicle every other day for 6 weeks. A, Flowchart illustrating the experimental procedure. This figure was created using images from Photoshop and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/h76jjnw . B Representative photographs of atherosclerotic plaques in the aortic arches and their branches. Representative images and quantification of Oil Red O-stained aortas ( C , n = 8. Scale bar = 2 mm) and aortic roots ( D and E , n = 8. Scale bar = 200 µm). F Representative images of H&E and Masson’s trichrome-stained aortic roots. Scale bar = 200 µm. G Quantification of plaque area, percentage of necrotic core, and collagen of aortic roots ( n = 8 per group). H , I Immunohistochemistry of CD68 + macrophages and vulnerability index in the aortic root plaque of FIDAS-5 treated mice, n = 8 per group. Scale bar = 100 µm. J – R Representative images of female and male mice fed MRD or CD for 6 weeks after a 10-week HFD. J Schematic figure showing the experimental strategy and subsequent analysis. This figure was created using images from Photoshop and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/h76jjnw . K Representative images of aortic arches and their branches in the indicated group. Representative images and quantification of Oil Red O-stained aortas ( L , n = 8. Scale bar = 2 mm) and aortic roots ( M and N , n = 8. Scale bar = 200 µm). O Representative images of H&E and Masson’s trichrome-stained aortic root. P Quantification of plaque area, percentage of necrotic core, and collagen, n = 8. Scale bar = 200 µm. Q and R Immunohistochemical staining CD68 + macrophages and vulnerability index, n = 8. Scale bar = 100 µm. Data are presented as mean ± SD and comparisons were made using unpaired Student’s t -test; two-tailed P values are shown. 8-week-old female and male ApoE -/- mice were used. FIDAS-5, a MAT2A inhibitor; MRD, methionine-restricted diet. Source data are provided as a Source Data file.

Techniques: Staining, Immunohistochemistry, Immunohistochemical staining, Two Tailed Test

A Norepinephrine levels in serum from TCFA-positive and TCFA-negative individuals ( n = 38 independent experiments). B Correlation between serum the ratio of SAM/SAH and norepinephrine levels. C The percentage of patients presenting with TCFA in 3 coronary arteries varied according to their levels of the SAM/SAH ratio and norepinephrine. D MAT2A expression in peripheral blood monocytes from 6-OHDA-treated ApoE -/- mice ( n = 3, one representative experiment out of three was shown). E Representative images and quantification of H&E and Oil Red O staining in aortic root treated with 6-OHDA (250 mg/kg) and AAV-MAT2A, n = 6. Scale bar = 100 µm. F Immunoblots of aortic plaques from ApoE -/- mice treated with 6-OHDA ( n = 3). G , Mat2a mRNA expression in BMDMs pre-treated with 20 nM RAPA followed by 10 mM norepinephrine ( n = 6, one representative experiment out of three was shown). H Transcript levels of c-Myc and Mat2a in BMDMs transfected with the indicated siRNAs ( n = 6). I Occupancy analysis of c-MYC by ChIP-qPCR in BMDMs treated with DMSO vehicle or RAPA (20 nM) ( n = 6). A Two-tailed Mann–Whitney P -values are indicated; Data are shown as median with IQR. B Pearson correlation coefficient test was used; the regression coefficients and two-tailed P -values are shown. C Chi-squared test was used; Data are shown as %. D – F Unpaired Student’s t -test was used; the two-tailed P -values are shown; Data are presented as mean ± SD. G , I Two-way ANOVA was used; The adjusted P -values are shown; Data are presented as mean ± SD. H One-way ANOVA was used; The adjusted P -values are shown. 8-week-old female and male ApoE -/- mice were used. Data are presented as mean ± SD. AAV adeno-associated virus, RAPA rapamycin, 6-OHDA 6-Hydroxydopamine. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages

doi: 10.1038/s41467-025-66121-z

Figure Lengend Snippet: A Norepinephrine levels in serum from TCFA-positive and TCFA-negative individuals ( n = 38 independent experiments). B Correlation between serum the ratio of SAM/SAH and norepinephrine levels. C The percentage of patients presenting with TCFA in 3 coronary arteries varied according to their levels of the SAM/SAH ratio and norepinephrine. D MAT2A expression in peripheral blood monocytes from 6-OHDA-treated ApoE -/- mice ( n = 3, one representative experiment out of three was shown). E Representative images and quantification of H&E and Oil Red O staining in aortic root treated with 6-OHDA (250 mg/kg) and AAV-MAT2A, n = 6. Scale bar = 100 µm. F Immunoblots of aortic plaques from ApoE -/- mice treated with 6-OHDA ( n = 3). G , Mat2a mRNA expression in BMDMs pre-treated with 20 nM RAPA followed by 10 mM norepinephrine ( n = 6, one representative experiment out of three was shown). H Transcript levels of c-Myc and Mat2a in BMDMs transfected with the indicated siRNAs ( n = 6). I Occupancy analysis of c-MYC by ChIP-qPCR in BMDMs treated with DMSO vehicle or RAPA (20 nM) ( n = 6). A Two-tailed Mann–Whitney P -values are indicated; Data are shown as median with IQR. B Pearson correlation coefficient test was used; the regression coefficients and two-tailed P -values are shown. C Chi-squared test was used; Data are shown as %. D – F Unpaired Student’s t -test was used; the two-tailed P -values are shown; Data are presented as mean ± SD. G , I Two-way ANOVA was used; The adjusted P -values are shown; Data are presented as mean ± SD. H One-way ANOVA was used; The adjusted P -values are shown. 8-week-old female and male ApoE -/- mice were used. Data are presented as mean ± SD. AAV adeno-associated virus, RAPA rapamycin, 6-OHDA 6-Hydroxydopamine. Source data are provided as a Source Data file.

Techniques: Expressing, Staining, Western Blot, Transfection, ChIP-qPCR, Two Tailed Test, MANN-WHITNEY, Virus

A Study design in the validation cohort. This figure was created using images from PowerPoint and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/qbkjhvs . Detection of monocytes SAM and SAH concentrations ( B ), and SAM/SAH ratio ( C ) of TCFA-positive and TCFA-negative individuals ( n = 100 subjects). D Serum norepinephrine levels from TCFA-positive and TCFA-negative individuals ( n = 100 independent experiments). Qualitative and quantitative OCT analysis of vulnerable plaque characteristics between patients with high and low SAM/SAH levels ( E ) or with high and low norepinephrine levels ( F ) ( n = 100 independent experiments). Pearson correlation analysis of monocytes SAM/SAH ratio ( G ) or serum norepinephrine levels ( H ) with the thinnest FCT and mean lipid arc. I Two-tailed Pearson’s linear regression analysis between the SAM/SAH ratio and norepinephrine levels. J Multivariate logistic regression analysis depicting the relationship between the SAM/SAH ratio, norepinephrine levels, and TCFA ( n = 200 for total subjects). K Receiver operating characteristic curve of SAM/SAH, norepinephrine, and combined both for TCFA. L HR for incident 5-year MACE based on multivariable Cox proportional hazards regression analysis. Adjusted for age, gender, traditional coronary risk factors, and statin at discharge ( n = 200 for total subjects). M A Kaplan-Meier survival curve plots the 5-year MACE-free survival among 4 subgroups. N MAT2A-mediated monocyte methionine metabolism is closely associated with the presence of TCFA in patients. MAT2A, which is induced by the norepinephrine–mTOR–c-MYC axis, is critical for endowing monocytes/macrophages with proinflammatory state and migratory capacity during the development of atherosclerosis through H3K4me3 modification. Myeloid-specific MAT2A ablation, pharmacological blockade with FIDAS-5, or a low-methionine diet attenuate monocyte/macrophage inflammation and migration, thereby reducing atherosclerotic progression and plaque vulnerability. This figure was created using images from PowerPoint and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/gylosq5 . B – D Two-tailed Mann–Whitney P -values are indicated. E , F The box shows the 25th, 50th and 75th percentiles of the data. The whiskers represent minimum and the maximum. Data are presented as % or median with IQR, Chi-squared test or Mann-Whitney test was used, and two-tailed P -values were calculated. G – I Pearson correlation coefficient test was used; the regression coefficients and two-tailed P -values are shown. J Data points indicate OR, and 95% confidence intervals are represented by line length; two-tailed P -values are shown. K The 95% confidence interval is shown between brackets. L Data points indicate HR and 95% CI were represented by line length. M P -values were calculated with log rank test. HR hazard ratio. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages

doi: 10.1038/s41467-025-66121-z

Figure Lengend Snippet: A Study design in the validation cohort. This figure was created using images from PowerPoint and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/qbkjhvs . Detection of monocytes SAM and SAH concentrations ( B ), and SAM/SAH ratio ( C ) of TCFA-positive and TCFA-negative individuals ( n = 100 subjects). D Serum norepinephrine levels from TCFA-positive and TCFA-negative individuals ( n = 100 independent experiments). Qualitative and quantitative OCT analysis of vulnerable plaque characteristics between patients with high and low SAM/SAH levels ( E ) or with high and low norepinephrine levels ( F ) ( n = 100 independent experiments). Pearson correlation analysis of monocytes SAM/SAH ratio ( G ) or serum norepinephrine levels ( H ) with the thinnest FCT and mean lipid arc. I Two-tailed Pearson’s linear regression analysis between the SAM/SAH ratio and norepinephrine levels. J Multivariate logistic regression analysis depicting the relationship between the SAM/SAH ratio, norepinephrine levels, and TCFA ( n = 200 for total subjects). K Receiver operating characteristic curve of SAM/SAH, norepinephrine, and combined both for TCFA. L HR for incident 5-year MACE based on multivariable Cox proportional hazards regression analysis. Adjusted for age, gender, traditional coronary risk factors, and statin at discharge ( n = 200 for total subjects). M A Kaplan-Meier survival curve plots the 5-year MACE-free survival among 4 subgroups. N MAT2A-mediated monocyte methionine metabolism is closely associated with the presence of TCFA in patients. MAT2A, which is induced by the norepinephrine–mTOR–c-MYC axis, is critical for endowing monocytes/macrophages with proinflammatory state and migratory capacity during the development of atherosclerosis through H3K4me3 modification. Myeloid-specific MAT2A ablation, pharmacological blockade with FIDAS-5, or a low-methionine diet attenuate monocyte/macrophage inflammation and migration, thereby reducing atherosclerotic progression and plaque vulnerability. This figure was created using images from PowerPoint and BioRender. Created in BioRender. wan, p. (2025) https://BioRender.com/gylosq5 . B – D Two-tailed Mann–Whitney P -values are indicated. E , F The box shows the 25th, 50th and 75th percentiles of the data. The whiskers represent minimum and the maximum. Data are presented as % or median with IQR, Chi-squared test or Mann-Whitney test was used, and two-tailed P -values were calculated. G – I Pearson correlation coefficient test was used; the regression coefficients and two-tailed P -values are shown. J Data points indicate OR, and 95% confidence intervals are represented by line length; two-tailed P -values are shown. K The 95% confidence interval is shown between brackets. L Data points indicate HR and 95% CI were represented by line length. M P -values were calculated with log rank test. HR hazard ratio. Source data are provided as a Source Data file.

Techniques: Biomarker Discovery, Two Tailed Test, Modification, Migration, MANN-WHITNEY

Journal: Cell reports

Article Title: IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation

doi: 10.1016/j.celrep.2025.116330

Figure Lengend Snippet: (A) Western blot analysis of histone methylation (H3K4me1 and H3K4me4) in SEM and Lin− MLL-Af4 cells, control or depleted for IGF2BP3; n = 3. (B) Dot blot analysis of m 6 A modification (left) and methylene blue staining in SEM cells, control or depleted for IGF2BP3. (C) ELISA measurement of m 6 A modification on RNA isolated from SEM, Lin− MLL-Af4, and NALM6 cells ( n = 4 for SEM and Lin− MLL-Af4, n = 5 [sg5 = 3] for NALM6). (D) Bar plot (left) and pie chart (right) depicting the m 6 A peak distribution across genomic locations from the m 6 A-eCLIP data in SEM control and IGF2BP3-depleted cells. (E) Metagene plots depicting the changes in the m 6 A peak coverage across the transcriptome in SEM control and IGF2BP3-depleted cells. (F) Volcano plot (top) for genes showing differential m 6 A RNA methylation after IGF2BP3 depletion and IGF2BP3 targets defined by eCLIP analysis. Gray dashed lines indicate the significant cutoffs for differential expression (±1) and the adjusted p value (0.05). Hypomethylated genes are highlighted in blue, while hypermethylated genes are highlighted in red. IGV browser snapshots (bottom) of m 6 A-eCLIP depicting the coverage and change in the peak height between the NT and IGF2BP3-depleted cells for MAT2A 3′ UTR are shown. All data are n ≥ 3 replicates represented as mean ± standard deviation (SD), compared by two-sided unpaired t test; * p < 0.05, ** p < 0.01, and *** p < 0.001. In case of missing or outlier values, the replicate was not reported. All experiments were repeated at least twice for consistency. All the western blots were repeated at least three times to report the changes, if any. Refer also to .

Article Snippet: MAT2A , Proteintech , 55309-1-AP; RRID: AB_2881303.

Techniques: Western Blot, Methylation, Control, Dot Blot, Modification, Staining, Enzyme-linked Immunosorbent Assay, Isolation, Quantitative Proteomics, Standard Deviation

Journal: Cell reports

Article Title: IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation

doi: 10.1016/j.celrep.2025.116330

Figure Lengend Snippet: (A) Western blot analysis of Lin− cells from Igf2bp3 del/del mice. Briefly, cells were isolated from mice with a germline deletion of Igf2bp3, transformed with MLL-Af4, and then subjected to transduction with MSCV-based constructs carrying the wild-type murine Igf2bp3. Proteins that were analyzed are Igf2bp3, Mat2a, Mat2b, and actin. (B) Cell growth, measured by CellTiter-Glo, over 4 days in Igf2bp3 del/del Lin− MLL-Af4 cells with enforced IGF2BP3 expression as above. Viability has been normalized to control cells; mean ± standard deviation (SD) ( n = 5); one-way ANOVA followed by Bonferroni’s multiple comparisons test; **** p < 0.0001. (C) Representative Seahorse XF extracellular acidification rate (ECAR) kinetic trace in cells described above ( n = 4). (D) Aggregate lactate efflux rates from Seahorse XF analysis in cells described above; two-sided unpaired t test; * p < 0.05 ( n = 4). (E) Colony formation assays from Lin− MLL-Af4 cells as described above; two-sided unpaired t test; ** p < 0.01 ( n = 2). (F) ELISA measurement of m 6 A modification on RNA isolated from Igf2bp3 del/del Lin− MLL-Af4 cells with enforced IGF2BP3 expression as above; two-sided unpaired t test; * p < 0.05 ( n = 3). (G) Percentage engraftment of CD45.2 Lin− cells in bone marrow from Igf2bp3 del/del mice transduced with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (H) Quantitation of bone marrow count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (I) Spleen weights of mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (J) Quantitation of spleen cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (K) Quantitation of bone marrow CD11b+ cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (L) Quantitation of bone marrow Lin− cell count along with representative fluorescence-activated cell sorting (FACS) plots in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (M) Quantitation of bone marrow CD11b+cKit+ cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (N) Quantitation of bone marrow LSK (Lin− cKit+Sca1−) cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (O) Quantitation of bone marrow CD11b+Sca1− (potential LIC ) cell count in mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. (P) Seahorse XF ECAR kinetic trace for bone marrow cells isolated from the empty vector (Ctrl) or IGF2BP3 re-expression group at 6 weeks ( n = 4, each group; for representation n = 2). (Q) Aggregate lactate efflux rates from Seahorse XF analysis in cells described above; reported as mean ± SD ( n = 4). (R) ELISA measurement of m 6 A RNA modifications in splenic tumors isolated from mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks; reported as mean ± SD; 8 mice/group. (S) H&E staining of spleen of mice transplanted with mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups at 6 weeks. Scale bar: 100 μm. (T) Overall survival of mice transplanted with MLL-Af4 re-expressing empty vector (Ctrl) or IGF2BP3 in the two groups (representative graph cumulative of two experiments, 8 mice/group; the experiment was terminated after 12 weeks; Kaplan-Meier method with log rank test was used to report the results). The animal experiments were repeated twice. All the western blots were repeated at least three times to report the changes, if any. Data in this figure are represented as mean ± SD with n = 8 mice per group. Statistical tests were performed using two-sided unpaired t test with significance levels as indicated; * p < 0.05, ** p < 0.01, and *** p < 0.001. Refer also to and .

Article Snippet: MAT2A , Proteintech , 55309-1-AP; RRID: AB_2881303.

Techniques: Western Blot, Isolation, Transformation Assay, Transduction, Construct, Expressing, Control, Standard Deviation, Enzyme-linked Immunosorbent Assay, Modification, Plasmid Preparation, Quantitation Assay, Cell Counting, Fluorescence, FACS, Staining

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