Extended Data Fig. 6: 4-oxo-RA safeguards HSCs upon MI.
a, Volcano plots of DEGs between 4-oxo-RA and DMSO (vehicle) treatment depicted for cardiac monocytes, macrophages, fibroblasts and endothelial cells. b, Detailed experimental design to characterize HSC response after in vivo 4-oxo-RA treatment following MI. Readouts are shown at precise time points throughout acute, reparative and chronic phases of MI. c, GSEA of Reactome pathways in 4-oxo-RA vs. vehicle BM HSC cluster upon MI based on scRNA-seq. d, Flow cytometry-based plots, illustrating the percentage of BM lineage-traced dTomatopos lymphoid cells upon MI or sham surgery and treatment in our short equilibrium tracing. Data is presented as mean with standard deviation in different timepoints. Ordinary two-way ANOVA. n = 3–4. e, Flow cytometry-based plots, illustrating the percentage of BM lineage-traced dTomatopos lymphoid cells upon MI or sham surgery and treatment in our standard equilibrium tracing. Data is presented as mean with standard deviation. Ordinary two-way ANOVA. n = 3–4. f, 1st and 2nd plating of HSC CFU assay comparing sham, vehicle and 4-oxo-RA conditions upon MI. Ordinary one-way ANOVA. n = 7–11. g, Representative gating scheme for flow cytometric analysis of HSC transplantation assay of 4-oxo-RA and vehicle condition. Percentage of CD45.2 PB chimerism was monitored over a time course of 16 weeks. Percentage of donor-derived lineage bias in B-cells, myeloid cells and T-cells was quantified at 16 weeks in BM. h, Flow cytometric analysis of donor-derived (CD45.2) lineage bias in B-cells, myeloid cells and T-cells in PB and BM at 16 weeks post transplantation. Ordinary two-way ANOVA. n = 8–10. In (c, e), cells were isolated in the acute phase at day 3 after MI. Data are presented as mean ± standard deviation. n indicates the number of biological replicates per condition. For (a, e and f), two or more independent experiments were performed.
