Fig. 4: Senescent pericytes stimulate inflammatory macrophages through SASP factors and mitochondrial transfer.
From: A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models
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.
