APLNR marks a cardiac progenitor derived with human induced pluripotent stem cells

Abstract

<p>Cardiomyocytes can be readily derived from human induced pluripotent stem cell (hiPSC) lines,<br>yet its efficacy varies across different batches of the same and different hiPSC lines. To unravel the<br>inconsistencies of in vitro cardiac differentiation, we utilized single cell transcriptomics on hiPSCs<br>undergoing cardiac differentiation and identified cardiac and extra-cardiac lineages throughout<br>differentiation. We further identified APLNR as a surface marker for in vitro cardiac progenitors<br>and immunomagnetically isolated them. Differentiation of isolated in vitro APLNR+ cardiac<br>progenitors derived from multiple hiPSC lines resulted in predominantly cardiomyocytes<br>accompanied with cardiac mesenchyme. Transcriptomic analysis of differentiating in vitro<br>APLNR+ cardiac progenitors revealed transient expression of cardiac progenitor markers before<br>further commitment into cardiomyocyte and cardiac mesenchyme. Analysis of in vivo human and<br>mouse embryo single cell transcriptomic datasets have identified APLNR expression in early<br>cardiac progenitors of multiple lineages. This platform enables generation of in vitro cardiac<br>progenitors from multiple hiPSC lines without genetic manipulation, which has potential applications<br>in studying cardiac development, disease modelling and cardiac regeneration.<br></p>