Abstract
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 (m5C) deposition in RNA m5C 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 m5C profiles and transcriptome-wide expression facilitated the identification of m5C sites coupled to the cardiomyocyte differentiation and RNA-dependent regulatory mechanisms of stem cell pluripotency. The RNA m5C profiles in this dataset allow the evaluations of the m5C level and distribution of specific m5C loci and facilitate understanding of the m5C epitranscriptomic landscape in biological functions of hPSC-CM beyond in vivo transplantation barriers.
Published Version
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