Cardiac fibroblast sub-types in vitro reflect pathological cardiac remodeling in vivo

Figures

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  Fig. 1. 12-gene expression profile distinguishes hearts from HF patients and organ donors. A) Hydroxyproline content of hearts of organ donors and non-ischemic HF patients (n:8/15; *: p less than 0.05). B) Picrosirius Red staining of heart sections of organ donors and non-ischemic HF patients (size bar 2 mm). C) tSNE plot of donors and HF hearts with expression of 82 fibrosis related genes as input. D) tSNE of plot of donors and HF hearts with expression of 12 fibrosis related genes expressed in fibroblasts as input. E) Heat map of donors and HF hearts for expression of 12 fibrosis related genes in fibroblasts. Color code indicates expression level relative to mean expression of gene across patients, red color indicates increased and blue color decreased expression. F) Table indicating the percentage of HF patients in cluster 1 and 2 with specific clinical features. The ratio indicates the enrichment of patients with these features in cluster 2. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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  Fig. 2. Different cell types in preparations of cardiac fibroblasts from mice cultured for 15 days in vitro. A) Experimental set up. B-G) UMAP plots for expression of indicated genes (color code indicates expression level).

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  Fig. 3. Different subpopulations of cardiac fibroblasts from mice cultured for 15 days in vitro. A) UMAP plot with colors indicating different indicated subpopulations in preparations of cardiac fibroblasts from mice culture for 15d in vitro. (Numbers in brackets indicate size of subpopulation). B) UMAP plot with colors indicating cell cycle phase of cells. C) Dot plot representing expression of indicated genes in fibroblast subpopulations FB1-FB6. ED) RNA velocity plot with arrows indicating the calculated direction of development. E) Dot plots representing expression of Tgfb1/2/3 in different subpopulations of the cultured primary cells (EC: endothelial cells; FB1-FB6: fibroblasts; MP1-MP2: macrophages).

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  Fig. 4. Heat map of the top 10 expressed genes in each subpopulation identified in the preparations of cardiac fibroblasts from mice cultured for 15d in vitro. (FB1-FB6: fibroblasts; MP1-MP2: macrophages; EC: endothelial cells; color code indicates expression level).

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  Fig. 5. Fibroblast subpopulation marker cluster well different stages of a murine myocardial infarct model. A-D) PCA of indicated fibroblast subpopulation markers or all genes (C) results in clustering of different disease stages of murine myocardial infarct model published by Fu et al. (2018). Colors indicate disease stages. The percentage of variation represented by the PC is indicated.

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  Fig. 6. Stage specific expression of fibroblast marker genes in a murine myocardial infarct model. A) Heatmap for top10 marker genes for FB1-FB6. B) Heatmap for 12-gene HF expression profile. Color indicates expression level relative to mean expression of a gene across samples, red color indicates increased and blue color decreased expression. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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  Supplementary figure 1.

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  Supplementary figure 3.

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  Supplementary figure 6.