Journal: bioRxiv

Article Title: Context-dependent regulatory variants in Alzheimer’s disease

doi: 10.1101/2025.07.11.659973

Figure Lengend Snippet: (a) Differential expression analyses confirm significant up- or downregulated genes under various stimulation conditions (FDR < 0.05, DESeq2). (b) Gene set enrichment analyses of resting and stimulated THP-1 macrophages reveal immune-related shifts (IFN-β, IFN-γ, LPS+IFN-γ) that mirror ATAC-seq changes in . (FDR < 0.05, fast gene set enrichment analysis). (c) PCA of RNA-seq data shows distinct transcriptomic clusters for each state, reflecting diverse immune states. (d) Microglial and macrophage markers were expressed in all conditions. (e) Differential expression of microglial-state marker genes (Sun et al. ) in stimulated THP-1 macrophages versus non-marker genes (two-sided Mann-Whitney U, Benjamini- Hochberg correction). Significance codes, Benjamini-Hochberg FDR: **** < 1 × 10⁻⁴; *** < 1 × 10⁻³; ** < 1 × 10⁻²; * < 0.05; NS, not significant. (f) Transcriptomic concordance between LPS + IFN-γ-stimulated THP-1 macrophages and amyloid-fibril-treated iPSC-microglia. Pearson’s r is calculated on the expression levels of genes that are differentially expressed in the amyloid-fibril model (Sun et al. ).

Article Snippet: HMC3 microglia-like cells (ATCC CRL-3304) were cultured in Microglial Cell Medium Kit (Accegen, ABI-TM009) and maintained at 37°C with 5% CO2.

Techniques: Quantitative Proteomics, RNA Sequencing, Marker, MANN-WHITNEY, Expressing

Journal: bioRxiv

Article Title: Context-dependent regulatory variants in Alzheimer’s disease

doi: 10.1101/2025.07.11.659973

Figure Lengend Snippet: (a) Hi-C in THP-1 macrophages (<5-kb resolution) places the enhancer (black bar) in the same contact domain as the SEC63 promoter and shows a looping interaction with the OSTM1 promoter and a CTCF anchor in the intronic regions of AFG1L (b) Three-dimensional chromatin model of the SEC63-OSTM1 enhancer and nearby genes. (c) SEC63 , the enhancer, and OSTM1 knockdown in hyperinflammatory (LPS + IFN-γ- treated) THP-1 macrophages. (d) CRISPRi knockdown of the SEC63 and OSTM1 promoters perturbs distinct transcriptional pathways in resting and hyperinflammatory (LPS + IFN-γ-treated) THP-1 macrophages (fgsea, FDR<0.05). (e) Expression of the microglial-state marker genes defined by Sun et al. after CRISPRi. Silencing SEC63 shifts multiple microglial programs, and these shifts are amplified under LPS + IFN-γ-highlighting a central role for SEC63 in state transitions and immune responses.

Article Snippet: HMC3 microglia-like cells (ATCC CRL-3304) were cultured in Microglial Cell Medium Kit (Accegen, ABI-TM009) and maintained at 37°C with 5% CO2.

Techniques: Hi-C, Knockdown, Expressing, Marker, Amplification

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Pooled efficacy comparisons of ORR in patients who received Nab-PTX versus PTX in breast cancer therapy. The blue boxes signify the effect size for each individual study, with their size reflective of the weight assigned to each study in the analysis. The whiskers extending from each blue box delineate the 95% confidence interval (CI) for the effect size of the respective study. The odds ratio (OR) was calculated using a random-effects model. Statistical significance was assessed by a two-sided test, with P < 0.05 considered statistically significant. b Pooled efficacy comparisons of the pCR in patients who received Nab-PTX versus PTX in breast cancer therapy. The blue boxes signify the effect size for each individual study, with their size reflective of the weight assigned to each study in the analysis. The whiskers extending from each blue box delineate the 95% confidence interval (CI) for the effect size of the respective study. The odds ratio (OR) was calculated using a random-effects model. Statistical significance was assessed by two-sided test, with P < 0.05 considered statistically significant. c Schematic of experimental design for patient samples. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p d UMAP plot and bar graph showing identified cell clusters of infiltrated macrophages of breast cancer patient tissues with indicated treatment and their proportion in the indicated groups. e Box plots showing the TREM2 expression levels in macrophage subsets across the indicated experimental groups. Two-sided Wilcoxon test. In the box plots, the center line corresponds to the median, box corresponds to the interquartile range (IQR), and whiskers 1.5 × IQR. f Violin-box plots showing the TREM2 expression levels in identified cell clusters of infiltrated macrophages using the scRNA-seq data. g Representative immunofluorescence staining of tissues from patients who received PTX treatments or not. h Representative immunofluorescence staining of tissues from patients who received Nab-PTX treatments or not. ns, not significant. Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Expressing, Immunofluorescence, Staining

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Representative immunofluorescence staining of tissues from patients with and without lung metastases. b Quantification of TREM2-expressing macrophages in tissues from patients with and without lung metastases ( n = 5 patients per group). c Schematic of the experimental design in 4T1-Luc breast-tumor-bearing mice treated with DMSO or PTX. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p d Representative in vivo bioluminescence images of mice that received the indicated treatments ( n = 5 mice per group). e Representative bright-field images (left) and hematoxylin and eosin (H&E) staining (right) of lungs from mice injected orthotopically with 4T1-Luc cells and treated as described in ( c ) ( n = 5 mice per group). f Quantification (right) of the total numbers of lung-surface metastases ( n = 6 mice per group). g Representative flow cytometry analysis showing a histogram (left) and quantification (right) of the proportion of TREM2-expressing macrophages in tumors ( n = 3 mice per group). h Representative immunofluorescence staining of tumors in mice that received the indicated treatments. i Schematic of Nab-PTX treatment in Py8119 breast tumor-bearing mice. Mice were intraperitoneally injected with DMSO, PTX, PBS, or Nab-PTX at the indicated times. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p j Photographs (left) of tumors in mice that received the indicated treatments on day 14. Tumor weights (right) of mice that received the indicated treatments ( n = 6 mice per group). k Tumor volumes (right) of mice that received the indicated treatments ( n = 6 mice per group). l Representative bright-field images (left) of lungs from mice that received the indicated treatments. Quantification of the total numbers of lung-surface metastases is shown (right) ( n = 6 mice per group). m Representative H&E-stained images of lungs from mice that received the indicated treatments. n , o Representative flow cytometric analysis of pseudo-color plots ( n ) and quantification ( o ) showing the proportion of TREM2-expressing macrophages in tumors ( n = 4 mice per group). Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( b , f and g ), two-sided one-way ANOVA followed by Tukey’s test ( j , l and o ) and two-sided two-way ANOVA followed by Tukey’s test ( k ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Immunofluorescence, Staining, Expressing, In Vivo, Injection, Flow Cytometry

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Schematic of the experimental setup with THP1 or Raw264.7 cells with indicated treatment. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p b Quantification of proportion of TREM2 in THP1 and Raw264.7 cells with PTX. n = 3 biological independent samples. c Western blot of THP1 and Raw264.7 cells with indicated treatments. The experiment was independently repeated three times with similar results. d Schematic of the experimental strategy. CM was collected from tumor cells with the indicated treatment. TREM2 expression in macrophages incubated with the CM was assessed. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p e Quantification of proportion of TREM2 in THP1 incubated with CM of BT549 cells, SUM159 cells and MDA-MB-231 cells treated with PTX, in BMDM incubated with CM of Py8119 treated with PTX, in Raw264.7 incubated with CM from 4T1 and Py8119 cells treated with PTX, respectively. n = 3 biological independent samples. f Western blot analysis of TREM2 and related proteins in THP1, BMDMs, and Raw264.7 cells incubated with CM from BT549, SUM159, Py8119, and 4T1 cells, respectively. The experiment was independently repeated three times with similar results. g Representative immunofluorescence staining of THP1 cells incubated with BT549 CM. n = 3 biological independent samples. h Quantification of proportion of TREM2 in THP1 incubated with CM from BT549, SUM159, and MDA-MB-231 cells treated with Nab-PTX, respectively. n = 3 biological independent samples. i Quantification of the proportion of TREM2 in BMDM incubated with CM of Py8119 treated with Nab-PTX. n = 3 biological independent samples. j Cytokine array analysis of CM from BT549 cells treated indicated treatment. k Western blot analysis of the indicated proteins in Raw264.7 cells and BMDMs treated with recombinant FGF2. The experiment was independently repeated three times with similar results. l Quantification of the proportion of TREM2 in Raw264.7 cells and BMDMs treated with recombinant FGF2. n = 3 biological independent samples. m Schematic of the experimental strategy. CM was collected from tumor cells with the indicated treatment, and then pretreatment using an FGF2 neutralizing antibody. TREM2 expression in macrophages incubated with the CM was assessed. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p n Western blot analysis of the indicated proteins in Raw264.7 and BMDMs incubated with the indicated CM. The experiment was independently repeated three times with similar results. o Quantification of the proportion of TREM2 in Raw264.7 and BMDMs incubated with the indicated CM. n = 3 biological independent samples. p Representative multiplex immunofluorescence staining of CD68, TREM2 and FGF2 in tumors treated with PTX or Nab-PTX ( n = 3 mice per group). The experiment was independently repeated three times with similar results. Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( b , e , h and i ) and two-sided one-way ANOVA followed by Tukey’s test ( l and o ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Western Blot, Expressing, Incubation, Immunofluorescence, Staining, Recombinant, Multiplex Assay

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Overlap of RNA-seq ( n = 3) and PROMO public database analyses to predict transcription factors regulating TREM2 expression. b Correlations between FGF2 and ATF3 expression in breast cancer using TCGA databases. c qPCR analysis of Atf3 expression in the indicated cells. n = 4 (DMSO and PTX) or 3 (PBS and Nab-PTX) biological independent samples. d Western blot analysis of the indicated proteins in Py8119 cells transfected with ATF3-expressing or control vectors. The experiment was independently repeated three times with similar results. e qPCR analysis of Fgf2 expression in Py8119 cells transfected with Atf3 -expressing or control vectors. n = 3 biological independent samples. f Luciferase activity in HEK293T cells transfected with the indicated reporters and Atf3 -expressing or control vectors. n = 3 biological independent samples. g Abundance of Atf3 bound to the Trem2 promoter in Py8119 cells, as assessed by ChIP-qPCR. n = 3 biological independent samples. h ATAC-seq tracks showing the chromatin accessibility in the ATF3 loci for BT549 cells treated by PTX or Nab-PTX. n = 2 samples per group. Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( c, e and f ) and two-sided two-way ANOVA followed by Šídák’s test ( g ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: RNA Sequencing, Expressing, Western Blot, Transfection, Control, Luciferase, Activity Assay, ChIP-qPCR

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Overlap of GeneCards and EDCODE public databases analyses to predict transcription factors that regulate TREM2. b Western blot analysis of the indicated proteins in BMDMs and Raw264.7 cells incubated with FGF2 (left) and with CM from Py8119 cells treated with PTX (right). The experiment was independently repeated three times with similar results. c Western blot analysis of the indicated proteins in Raw264.7 cells incubated with the indicated treatment. The experiment was independently repeated three times with similar results. d qPCR analysis of Trem2 expression in BMDMs transfected with Egr1 -expressing vectors. n = 3 biological independent samples. e Western blot analysis of TREM2 expression in BMDMs transfected with Egr1 -expressing vectors. The experiment was independently repeated three times with similar results. f Luciferase activity of HEK293T cells transfected with the indicated reporters and EGR1 -expressing or control vectors. n = 3 biological independent samples. g Abundance of EGR1 bound to the TREM2 promoter in BMDMs assessed by ChIP-qPCR. n = 3 biological independent samples. h Schematic of the Transwell assay. The first CM was collected from tumor cells with indicated treatment, and the second CM was collected from macrophages incubated with the first CM. The migration and invasion capabilities of macrophages incubated with the first CM were assessed. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p i Quantification of migration and invasion of Py8119 cells induced by BMDM CM incubated with CM from Py8119 cells treated with PTX, and BT549, SUM159, and MDA-MB-231 cells induced by THP1 CM incubated with CM from BT549, SUM159, and MDA-MB-231 cells treated with PTX (left) or Nab-PTX (right), respectively. n = 5 biological independent samples. j Cytokine array analysis of CM from BMDMs with or without TREM2. k Quantification of migration and invasion of Py8119 cells incubated with indicated proteins. n = 3 biological independent samples. l Quantification of migration and invasion of Py8119 cells induced by CM from BMDMs ( Trem2 +/+ ) with CDE-096. n = 3 biological independent samples. m Western blot analysis of EMT- stimulating proteins in BMDMs incubated with indicated proteins. The experiment was independently repeated three times with similar results. n Schematic illustration showing that FGF2 promotes ERK1/2 phosphorylation to upregulate EGR1, which increases TREM2 expression in macrophages. Upregulated TREM2 enhances the secretion of Serpin E1, HGF, CCL3, and CXCL2 from macrophages to tumor cells, facilitating tumor metastasis via EMT. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p . Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( d, f, i and l ), two-sided one-way ANOVA followed by Tukey’s test ( k ) and two-sided two-way ANOVA followed by Šídák’s test ( g ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Western Blot, Incubation, Expressing, Transfection, Luciferase, Activity Assay, Control, ChIP-qPCR, Transwell Assay, Migration, Phospho-proteomics

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: PTX, but not Nab-PTX, promotes lung metastasis by inducing TREM2 + macrophage recruitment. Mechanistically, PTX enhances the ATF3-FGF2 axis in breast cancer cells; secreted FGF2 activates the EGR1–TREM2–EMT cytokine axis in macrophages. Created in BioRender. Xing, Y. (2026) https://BioRender.com/6hxlbow .

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques:

Journal: Molecular and Cellular Biology

Article Title: Regulation of Cell-Cell Adhesion by Abi/Diaphanous Complexes

doi: 10.1128/mcb.01483-08

Figure Lengend Snippet: FIG. 4. Formation of nascent junctions is independent of N-WASP. (A) A431 cells transfected with the indicated siRNAs were incubated with 4 mM EGTA for 30 min to dissolve junctions, washed, and then incubated for 1 h in medium containing 2 mM calcium to allow junctions to re-form. Cells were fixed and stained with anti--catenin antibody (bar, 10 m). (B) The percentages of cells with cell-cell junctions of randomly selected regions were analyzed. Results represent the means SEMs of at least three independent experiments, and at least 500 cells were counted in each experiment. *, P 0.01. (C) A431 cells were transfected with N-WASP siRNA or with a control siRNA. After 48 h, cells were lysed and cell lysates were analyzed by Western blotting with the indicated antibodies. (D) Abi preferentially interacts with Wave1 over N-WASP in A431 epithelial cells. A431 cells expressing EGFP-Wave1 or EGFP-N-WASP were lysed, and the endogenous Abi proteins were immunoprecipitated (IP) with the indicated anti-Abi1 or anti-Abi2 antibodies. The coimmunoprecipitated EGFP-Wave1 or EGFP-N-WASP was detected by Western blotting (IB) with anti-GFP antibodies. The levels of endogenous Abi1 and Abi2 are shown in the middle and bottom panels, respectively. Total lysates (Lys) were analyzed for expression of EGFP-Wave1 and EGFP-N-WASP by blotting with anti-GFP antibodies.

Article Snippet: Goat antibodies used were Wave2 (Santa Cruz Biotechnology, Santa Cruz, CA), Abi2 (Santa Cruz Biotechnology), and Dia2 (Santa Cruz Biotechnology).

Techniques: Transfection, Incubation, Staining, Control, Western Blot, Expressing, Immunoprecipitation

Journal: Autophagy

Article Title: A novel C. elegans model for MAPT/Tau spreading reveals genes critical for endolysosomal integrity and seeded MAPT/Tau aggregation

doi: 10.1080/15548627.2025.2551676

Figure Lengend Snippet: Knockdown of human orthologs of C. elegans screening hits modulates endolysosomal rupture in human HEK293T cells. (A) Schematic illustration of endolysosomal damage detection using the galectin-3 reporter (sfGFP-LGALS3) in HEK293T cells. (B) Representative collapsed confocal z-stacks (488 nm channel) of HEK293T cells stably expressing the sfGFP-LGALS3 reporter and the inducible dCas9 system, transiently transfected with either the empty vector control (pLG1) or pLG1 expressing sgRNAs targeting the indicated genes. Scale bar: 20 μm. (C) Quantification of LGALS3 foci in HEK293T cells stably expressing the sfGFP-LGALS3 reporter and the inducible dCas9 system, transiently transfected with either the empty pLG1 vector or pLG1 expressing sgRnas targeting the indicated genes. Downregulation of SERINC4 expression did not increase LGALS3 foci formation, while targeting the expression of all other genes significantly increased LGALS3 foci formation in the LGALS3 reporter cells. Data are presented as boxplot, showing the mean, upper and lower quartiles, and the minimum and maximum values. Points outside the min-max range represent outliers. N = 4 with 10–11 images per gene and replicate. Each point represents one image. Statistical analysis was conducted using two-way mixed-model ANOVA on rank-transformed data, with pairwise comparisons of estimated marginal means with Bonferroni correction for multiple comparisons. Color-coding corresponds to p-values as indicated in the figure legend.

Article Snippet: For inducible gene repression, a KRAB-Sp dCas9 PiggyBac-based construct (Addgene 84,241; deposited by Stanley Qi) was stably integrated into the HEK293T sfGFP-LGALS3 cells.

Techniques: Knockdown, Stable Transfection, Expressing, Transfection, Plasmid Preparation, Control, Transformation Assay