Figure 5: CTHRC1 is an essential effector of RCF for the healing repair process.
(A) Normalized expression bar plots (mean ± SD) of Cthrc1 in CF (GFP+/CD31−/CD45−), endothelial (CD31+), and bone marrow-derived cells (CD45+) at different time-points. (B) Localization of CTHRC1 (green) in the left ventricle of healthy wild type (WT) mice, and at 3, 5 and 7 dpi. Cardiac Troponin-I+ (cTN) cardiomyocytes (red), Nuclei (DAPI, blue). (C) Normalized expression bar plots (mean ± SD) of Cthrc1 in endothelial (CD31+), bone marrow-derived cells (CD45+), CF (mEFSK4+/CD31−/CD45−) and cardiomyocytes from WT hearts at 5dpi, linear model with normalized counts. (D) Kaplan-Meier survival curves after MI in WT and Cthrc1 knockout (KO) mice. Log-rank Mantel-Cox test, n=10 per group. (E) Representative images of collagen deposition in left ventricle of WT (left) and KO (right) mice. Quantification of collagen deposition in the LV in both genotypes at 3dpi (WT, open circle; KO, closed circle), unpaired t-test (right). (F) Volcano plots showing differential gene expression between WT and KO CF at 5dpi. (G) Dot plot comparison of enriched pathways in the bulk RNA-seq analysis between Cthrc1-KO (left column) and WT (right column) at 7dpi. (H) t-SNE representation of 4,189 CF from one KO heart at 7dpi. Red dots represent RCF-like fibroblasts, and the number the percentage of them in relation to the total isolated CF. t-SNE representation for RCF markers (below). (I) Proportion of cluster B CF in each of the datasets. ** p≤0.01, *** p≤0.001. KO = knockout; WT = wild type.