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Okubo, Chikako; Narita, Megumi; Inagaki, Azusa; Nishikawa, Misato; Hotta, Akitsu; Yamanaka, Shinya; Yoshida, Yoshinori
Stem cell reports, 08/2021, Volume: 16, Issue: 8Journal Article
Hand1 and Hand2 are transcriptional factors, and knockout mice of these genes show left and right ventricular hypoplasia, respectively. However, their function and expression in human cardiogenesis are not well studied. To delineate their expressions and assess their functions in human cardiomyocytes (CMs) in vitro, we established two triple-reporter human induced pluripotent stem cell lines that express HAND1mCherry, HAND2EGFP and either MYH6-driven iRFP670 or tagBFP constitutively and investigated their expression dynamics during cardiac differentiation. On day 5 of the differentiation, HAND1 expression marked cardiac progenitor cells. We profiled the CM subpopulations on day 20 with RNA sequencing and found that mCherry+ CMs showed higher proliferative ability than mCherry− CMs and identified a gene network of LEF1, HAND1, and HAND2 to regulate proliferation in CMs. Finally, we identified CD105 as a surface marker of highly proliferative CMs. Display omitted •Expression of HAND1 marks cardiovascular progenitor cells•LEF1 is a key regulator of proliferating cardiomyocytes•CD105 expression marks highly proliferative cardiomyocytes HAND1 and HAND2 are important cardiac transcriptional factors, but their functions in human cardiogenesis are difficult to analyze. Okubo et al. established HAND1mCherry and HAND2EGFP reporter induced pluripotent stem cells and showed that HAND1 marks cardiovascular progenitors and regulates the gene network of cardiomyocyte proliferation. They further showed that CD105 can be used as a surface marker for proliferative cardiomyocytes.
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