Single-Cell sequence profile in human cardiomyocytes differentiated from Wt and QKI mutant embryonic stem cells

Transcriptomic profiling of WT and QKI KO hESC derived cardiomyocyte on Day 6 and 15 via Single cell RNA-seq. To gain insight into the role of QKI on cardiac lineage commitment,we applied a widely used cardiomyocyte differentiation protocol that was reported to produce a population of more than 90% cardiac troponin T (TNNT2)-positive cardiomyocytes. Following, we performed single-cell RNA-sequencing (scRNA-seq) on over 6,500 cells captured across two key time points (Day 6 and 15) during in vitro cardiac differentiation of human ESCs. When comparing the overall distribution of differentiated cells derived from QKI null hESCs and normal control hESCs at Day-6 and -15, we did not observe a major defect in terms of different cell lineages, suggesting that the lineage specification and determination towards cardiomyocytes were well preserved in hESCs-QKIdel. When we compared the expression profiles of these clusters, we did find the expression of 13 genes which involved in sarcomere formation was significantly altered. These downregulation of sarcomere genes may lead to the dimished contractile function of hESCs-QKIdel derived cardiomyocytes.