Fig. 4: MiR-365 regulates the key repolarizing potassium channels in ventricular myocytes.

a Schematic overview of the single-cell RNA-sequencing experiment in healthy hiPSC-CMs treated with mimic- or antimiR-365. b Uniform manifold approximation and projection (UMAP) plot representing the unbiased clustering of 6000 transcriptomes revealed three main populations of cells, namely ventricular-like, atrial-like, and other cardiac myocytes. c Dot plot showing the expression of marker genes defining each subpopulation of hiPSC-CMs. d Combined UMAP clustering of hiPSC-CM treated with mimic- or antimiR-365 to depict the contribution of cells from each sample to different hiPSC-CM clusters (left panel). Violin plots representing the expression changes of ion channel targets of miR-365 in ventricular-like cardiac myocytes upon manipulation of miR-365 (right panel). Analyses were performed using CellRanger and Seurat (v3.2) packages. Adjusted P-value was calculated using two-sided Wilcoxon Rank Sum test for each gene. e Contribution of the validated targets of miR-365 in different phases of ventricular myocyte AP. Solid lines represent miR-365-based regulation at the transcriptome level, while the dotted lines depict a potential interaction between miR-365 and the ion channel mRNAs without a relevant change at mRNA level.