Journal: Frontiers in Immunology

Article Title: Integrated single-cell and spatial transcriptomics reveal the differentiation drivers of gastric epithelial lineage progression

doi: 10.3389/fimmu.2026.1712830

Figure Lengend Snippet: Pseudotime trajectory reveals a normal-to-cancer epithelial transition with elevated UPP1 expression. (A) Diagram of gastric epithelial lineages, including intestinal metaplasia and gastric cancer. (B) CytoTRACE analysis showing differentiation states of epithelial subtypes. (C) UMAP plots with epithelial subtype annotations based on canonical markers, including intestinal markers (OLFM4, MUC2, CDX2) and mucous cell markers (MUC5AC, MUC6). (D) Identification of highly differentiated cell population as a transitional population between normal and malignant epithelial cells. (E–G) Pseudotime trajectories showing progression from non-neoplastic to cancer epithelial cells. (H) Schematic summarizing GC transition and HP-related inflammation–cancer progression. (I, J) UPP1 expression along pseudotime in tumorigenesis differentiation. (K) UPP1 expression trends in different epithelial subtypes. (L) UMAP visualization of UPP1 expression distribution.

Article Snippet: AGS and HGC27 cells were transfected with control or target siRNAs (Proteinbio) or plasmids for UPP1 overexpression/shRNA knockdown (GeneCopoeia) using Lipofectamine 3000 (Invitrogen) per manufacturer’s protocol.

Techniques: Expressing

Journal: Frontiers in Immunology

Article Title: Integrated single-cell and spatial transcriptomics reveal the differentiation drivers of gastric epithelial lineage progression

doi: 10.3389/fimmu.2026.1712830

Figure Lengend Snippet: UPP1 regulate intestinal metaplasia development in human gastric organoids. (A) Spatial annotation of normal and IM regions, showing IM proximity to surface mucous cells. (B) Pseudotime trajectory from normal epithelium to IM, with UPP1 expression increasing along the path. (C) NMF clustering of gastric epithelial cells identifying four major meta-programs (MPs). (D) Definition of MPs by their top 50 genes, corresponding to epithelial feature, cell cycle/stemness, metabolism and stress/inflammation. (E) MP activity scoring across epithelial cells, showing that metabolic and stress-response programs are strongly enriched in IM and tumor epithelial populations.

Article Snippet: AGS and HGC27 cells were transfected with control or target siRNAs (Proteinbio) or plasmids for UPP1 overexpression/shRNA knockdown (GeneCopoeia) using Lipofectamine 3000 (Invitrogen) per manufacturer’s protocol.

Techniques: Expressing, Activity Assay

Journal: Frontiers in Immunology

Article Title: Integrated single-cell and spatial transcriptomics reveal the differentiation drivers of gastric epithelial lineage progression

doi: 10.3389/fimmu.2026.1712830

Figure Lengend Snippet: UPP1 is overexpressed in gastric cancer and promotes tumor proliferation and invasion. (A) TCGA-STAD analysis showing higher UPP1 expression in gastric cancer tissues compared with normal tissues. (B) Kaplan–Meier survival curve stratified by UPP1 expression level. (C) UPP1 mRNA levels in normal gastric epithelial cells (GES-1) and gastric cancer cell lines. (D–F) Association between UPP1 expression and pathological TNM stage. (G) Immunohistochemistry from Human Protein Atlas showing low UPP1 in normal tissue and high expression in gastric cancer. (H) Functional assays in AGS and HGC27 cells showing reduced clonogenicity and migration after UPP1 knockdown. *p < 0.05; **p < 0.01; ***p < 0.001.

Article Snippet: AGS and HGC27 cells were transfected with control or target siRNAs (Proteinbio) or plasmids for UPP1 overexpression/shRNA knockdown (GeneCopoeia) using Lipofectamine 3000 (Invitrogen) per manufacturer’s protocol.

Techniques: Expressing, Immunohistochemistry, Functional Assay, Migration, Knockdown

Journal: Frontiers in Immunology

Article Title: Integrated single-cell and spatial transcriptomics reveal the differentiation drivers of gastric epithelial lineage progression

doi: 10.3389/fimmu.2026.1712830

Figure Lengend Snippet: UPP1 promotes intestinal metaplasia in gastric epithelial organoid models. (A) Single-cell RNA-seq analysis of gastric organoids with initial epithelial clustering and annotation. (B) UPP1 expression across epithelial subtypes, enriched in IM-like cells. (C) Feature plot showing UPP1 distribution in UMAP space. (D) Western blot analysis of UPP1 in patient-derived normal, IM, and gastric cancer tissues. (E) Gastric and intestinal scores for UPP1-high vs. UPP1-low cells. (F) Organoid experiments showing increased IM-like morphology under WNT-depleted conditions, further enhanced by UPP1 knockout.

Article Snippet: AGS and HGC27 cells were transfected with control or target siRNAs (Proteinbio) or plasmids for UPP1 overexpression/shRNA knockdown (GeneCopoeia) using Lipofectamine 3000 (Invitrogen) per manufacturer’s protocol.

Techniques: Single Cell, RNA Sequencing, Expressing, Western Blot, Derivative Assay, Knock-Out

Journal: Frontiers in Immunology

Article Title: Integrated single-cell and spatial transcriptomics reveal the differentiation drivers of gastric epithelial lineage progression

doi: 10.3389/fimmu.2026.1712830

Figure Lengend Snippet: Helicobacter pylori infection alters gastric epithelial differentiation trajectory and induces UPP1 expression. (A) UMAP of epithelial cells from HP + and HP - samples. (B) Cell-type annotations of HP + and HP - epithelial populations, including NE cells, normal epithelial cells, and cancer-like epithelial cells. (C) HP + pseudotime trajectory analysis identifying two differentiation paths: toward NE and toward cancer-like epithelium. (D) HP - pseudotime trajectories for comparison. (E) UPP1 expression along the malignant differentiation path in HP + samples. (F) Rapid urease test confirming HP infection in clinical specimens. (G) qPCR validation showing higher UPP1 expression in HP + tissues compared with HP - tissues. ***p < 0.001.

Article Snippet: AGS and HGC27 cells were transfected with control or target siRNAs (Proteinbio) or plasmids for UPP1 overexpression/shRNA knockdown (GeneCopoeia) using Lipofectamine 3000 (Invitrogen) per manufacturer’s protocol.

Techniques: Infection, Expressing, Comparison, Biomarker Discovery

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: USP11 expression is upregulated in HCC.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques: Expressing

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: USP11 is associated with the proliferation and migration of HCC cells.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques: Migration

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: USP11 inhibits erastin-induced ferroptosis in HCC cells.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques:

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: USP11 is associated with the sensitivity of HCC cells to taxanes.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques:

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: USP11 stabilizes NRF2 through deubiquitination.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques:

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: USP11 inhibits erastin-induced ferroptosis in HCC cells through NRF2.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques:

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: USP11 inhibits the sensitivity of HCC cells to taxanes through NRF2.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques:

Journal: Translational Oncology

Article Title: USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation

doi: 10.1016/j.tranon.2025.102553

Figure Lengend Snippet: In vivo knockdown of USP11 inhibits tumor growth and promotes ferroptosis.

Article Snippet: To trigger ferroptosis, cells with either USP11 overexpression or USP11 knockdown were exposed to erastin (20 μM; HY-15763; MedChemExpress, USA), a ferroptosis inducer, for 24 hours.

Techniques: In Vivo, Knockdown

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

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

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

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

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

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

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

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