Fig. 2: Transgenic disruption of myeloid-specific mechanotransduction generates improved healing with reduced inflammation.
From: Targeting circulating mechanoresponsive monocytes and macrophages to reduce fibrosis
a, The mechanical strain device model was applied to WT mice subjected to NS (n = 3 biological replicates), WT mice subjected to mechanical S (n = 3 biological replicates) and mice with FAK genetically knocked out (KO) in myeloid (Lyz2+) cells (S KO, n = 4 biological replicates). b, Gross photography and quantification of scars (NS versus S WT ***P = 0.0002; NS versus S KO *P = 0.0279; S WT versus S KO **P = 0.0023). Scale bar, 2 mm. c, Picrosirius red staining of collagen tissue architecture in our groups and in unwounded skin (Uwd, n = 4 biological replicates). Scale bar, 200 µm. d, We used CurveAlign and CT-FIRE algorithms on Picrosirius red-stained images to determine length (NS versus S WT **P = 0.0039; S WT versus S KO ***P = 0.0003; S WT versus Uwd ****P < 0.0001) and alignment of fibres (NS versus S WT ***P = 0.0001; S WT versus S KO ***P = 0.0010; S WT versus Uwd ***P = 0.0008). Scale bar, 200 μm. px, pixels. e,f, UMAP embedding of all cells showing treatment groups (e) and cell types (f). g,h, UMAP embedding of myeloid cells (g) with violin plots of top genes differentiating mechanoresponsive myeloid groups (h). i,j, UMAP embedding of fibroblasts (i) with Violin plots of top differentiating genes (j). k,l, CellChat interaction plots of macrophages and fibroblasts showing number of interactions (k) and interaction weights/strengths (l). Statistical comparisons made using one-way analysis of variance (ANOVA) with Tukey’s multiple comparisons tests of data shown as mean ± s.e.m. of biological replicates. Panel a created with BioRender.com.
