Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
Stem Cell Reports. 2021 Aug 10;16(8):1906-1922. doi: 10.1016/j.stemcr.2021.06.014. Epub 2021 Jul 22.
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 HAND1, HAND2 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.
Hand1 和 Hand2 是转录因子，这两种基因的敲除小鼠分别表现出左、右心室发育不全。然而，它们在人类心脏发生中的功能和表达尚未得到很好的研究。为了描述它们在体外人心肌细胞 (CMs) 中的表达，并评估其功能，我们建立了两个三重报告人诱导多能干细胞系，这些细胞系持续表达 HAND1、HAND2 和由 MYH6 驱动的 iRFP670 或 tagBFP，并研究了它们在心脏分化过程中的表达动态。在分化的第 5 天，HAND1 表达标记了心脏祖细胞。我们使用 RNA 测序对第 20 天的 CM 亚群进行了分析，发现 mCherry+CMs 的增殖能力高于 mCherry-CMs，并确定了一个调节 CM 增殖的 LEF1、HAND1 和 HAND2 基因网络。最后，我们鉴定出 CD105 是高增殖性 CM 的表面标志物。
