Fig. 4: Increased extrinsic tissue-scale forces activate Rac2 signalling in myeloid cells, which drives a Baker-IV fibrotic phenotype in mice. | Nature Biomedical Engineering

Fig. 4: Increased extrinsic tissue-scale forces activate Rac2 signalling in myeloid cells, which drives a Baker-IV fibrotic phenotype in mice.

From: Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells

Fig. 4

a, UMAP plot of myeloid cells in SM and MSI implant capsules. Clusters 1, 4 and 7 (red dotted line) are highly enriched in MSI capsules. b,c, FeaturePlot of top averaged Baker-IV markers (Fig. 1d), including key mechanotransduction and inflammatory chemokine signalling pathways (b) and Baker-I markers (c). Color bar denotes the amount of gene expression. d, Violin plots of Baker-IV markers differentially upregulated in the MSI clusters (arbitrary units). e, CODEX immunofluorescence staining of co-localized pixels of Rac2 and F4/80 (n = 3 independent capsules per group, *P = 0.0254). White box denotes high magnification (HM) image area. Scale bar for SM and MSI, 50 μm. Scale bar for HM images, 10 μm. Statistical comparisons for e were made by using a two-tailed t-test. Data are presented as mean ± s.e.m. f, Selected pathways significantly upregulated in murine MSI samples analysed using DAVID. Pathways highlighted in red are also upregulated in Baker-IV human specimens.

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