Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation

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 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.

Keywords: HAND1; HAND2; cardiomyocyte; development; pluripotent stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Cycle / genetics
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Gene Regulatory Networks / genetics
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • RNA Interference
  • RNA-Seq / methods
  • Time Factors
  • Transcriptome / genetics*


  • Basic Helix-Loop-Helix Transcription Factors
  • HAND2 protein, human
  • Luminescent Proteins
  • helix-loop-helix protein, eHAND