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. 2017 Nov 27;128(1):233–247. doi: 10.1172/JCI95937

Figure 3. H3K27me3 accrual in DSCs prevents fibroblast activation/myofibroblast formation and wound healing in the decidua.

Figure 3

(A–C) RNA-Seq analysis of DSCs, MSCs, and USCs, and the relationship of gene expression to H3K27me3 marking. Distribution of mRNA expression differences (Padj < 0.05; n = 3 samples/group), binned into progressive 2-fold changes. *P < 5.6 × 10–3, significantly over- (orange) or underrepresented (gray) for DSC>MSC targets as compared with expectation. (D) DSC>MSC H3K27me3 targets within all genes with significantly different expression both between MSCs and USCs and between DSCs and USCs. (E) H3K27me3 marking and mRNA expression of DSC>MSC targets involved in fibroblast activation/myofibroblast formation. The 15 genes with rankings are from the upper left quadrant of D and encode the classical markers FAP (12), CXCL12 (12), THY1 (14), and PDGFRB (12), proteins with less extensive literature such as IGFBP-5 (45), C-type natriuretic peptide (46), P311 (13), CXCL16 (47), integrin α11 (13), PAR2 (48), TRPC3 (49), and IL-33 (50), and several Wnt-signaling regulators induced during fibrosis or themselves profibrotic (13, 51). Although their expression was not increased in MSCs compared with USCs, other DSC>MSC targets included Acta2 (α-SMA) (13) and Cspg6 (14), 2 other major myofibroblast markers, as well as Agtr1a (14), Irf5, Pdpn (12), Tcf21 (14), Trpc6 (14), and Zeb1 (12), encoding additional emerging markers or inducers (bottom set). (F–I) Impaired wound healing responses in the decidua. Paired horns of undecidualized uteri were left unmanipulated (F) or scratched along their inner surface with a needle (G). Note the autofluorescent RBCs at the wound site (arrow). Representative images from 5 mice. Artificial decidua were wounded via injection with EGFP-expressing lentiviruses. Note the extravascular RBCs but minimal α-SMA staining at an injection site (H); the nearby myometrium was α-SMA+ (I). Representative images from 52 injection sites from 4 mice. Mice were sacrificed 2 days after scratching/injection.