Fig. 1

Identification of hiPSC-CM subpopulations by single-cell RNA-seq. a Integrative analytical workflow for identifying distinct cellular populations from single-cell RNA-seq analyses. Associated signatures can subsequently be further interrogated using orthogonal single-cell and bulk techniques (genome editing, ChIP-seq targets, overexpression models, changes at the protein level) and functional assays (calcium handling, patch-clamp). b A monolayer cardiomyocyte differentiation protocol was used to assess how single-cell populations change over time. Single-cell RNA-seq was performed on day 0, day 5, day 14, and day 45 of differentiation and 10,376 cell states identified using the software ICGS and Seurat-CCA. c A t-SNE plot was generated using AltAnalyze to visualize the expression of ICGS associated markers during the different days of differentiation. Twenty distinct cell populations were observed and could be attributed to populations representing pluripotent stem cells (PSC), definitive endoderm (DE), mesoderm (MESO), ectoderm (ECTO), stromal, neural crest (NC), endothelial cells, and early, mid or late cardiomyocyte progenitors