Transcriptome-wide RNA 5-methylcytosine profiles of human iPSCs and iPSC-derived cardiomyocytes.

Cardiac regenerative therapy has recently progressed by reprogramming somatic cells into induced pluripotent stem cells (iPSCs) and advanced by large-scale differentiation-derived cardiomyocytes (hiPSC-CMs). However, repairing damaged cardiac tissues with hiPSC-CMs remains limited due to immune rejection, cardiac arrhythmias, and concerns over tumor formation after hiPSC-CM transplantation. Despite efforts in profiling epigenomic changes during cardiac differentiation, regulatory mechanisms underlying 5-methylcytosine (m(5)C) deposition in RNA m(5)C epitranscriptomic landscape during hiPSC-to-cardiomyocyte differentiation remain unclear. Herein, bisulfite RNA-sequencing analysis was conducted in human pluripotent stem cells (hPSCs) from three independent cellular origins, and their derived cardiomyocytes (hPSC-CM), metabolic-maturation of derived cardiomyocytes (hPSC-CM-lac) and biochemical-enhanced derived cardiomyocytes (hPSC-CM-TDI). Integrated analysis of differentially methylated RNA m(5)C profiles and transcriptome-wide expression facilitated the identification of m(5)C sites coupled to the cardiomyocyte differentiation and RNA-dependent regulatory mechanisms of stem cell pluripotency. The RNA m(5)C profiles in this dataset allow the evaluations of the m(5)C level and distribution of specific m(5)C loci and facilitate understanding of the m(5)C epitranscriptomic landscape in biological functions of hPSC-CM beyond in vivo transplantation barriers.