Extended Data Figure 7: Alteration of In-PDGFRα levels in vivo modulates FAP activity.
From: Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis
a, b, FAPs treated in vitro with pA-VMOs showed a downregulation of In-PDGFRα (n = 3) (a), whereas those treated with the 5′ss-VMO exhibited an upregulation of In-PDGFRα (n = 3) (b). c, d, In vivo treatment with 5′ss-VMO decreases FAP proliferation (n = 16) (c) with a corresponding decrease in cell count (n = 24) (d). Treatment with pA-VMOs does not lead to a significant change in proliferation (P = 0.42). e, f, GSEA of FAPs collected from tibialis anterior muscles treated with pA-VMOs (e) or the 5′ss-VMO (f), compared to control-treated samples, were analysed for enrichment of pathways in the Reactome database30,31. Top sets with a false discovery rate of less than 5% are shown. g, h, Ingenuity pathway analysis of top regulators of gene expression in FAPs treated with pA-AMOs (g) or the 5′ss-VMO (h) compared to control treatment. The top hits are shown, excluding those with the ‘molecular type’ designated as a chemical or drug. For a–d, n represents biological replicates of pooled FAPs. *P < 0.05; **P < 0.01, ***P < 0.001, ****P < 0.0001; unpaired Student t-tests. In g, h, two pooled FAP samples per condition were used with the overlap P-value calculated using the Fisher’s exact test. Error bars represent s.e.m.
