A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees

Elife. 2019 Apr 8:8:e42374. doi: 10.7554/eLife.42374.

Abstract

Despite anatomical similarities, there are differences in susceptibility to cardiovascular disease (CVD) between primates; humans are prone to myocardial ischemia, while chimpanzees are prone to myocardial fibrosis. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) allow for direct inter-species comparisons of the gene regulatory response to CVD-relevant perturbations such as oxygen deprivation, a consequence of ischemia. To gain insight into the evolution of disease susceptibility, we characterized gene expression levels in iPSC-CMs in humans and chimpanzees, before and after hypoxia and re-oxygenation. The transcriptional response to hypoxia is generally conserved across species, yet we were able to identify hundreds of species-specific regulatory responses including in genes previously associated with CVD. The 1,920 genes that respond to hypoxia in both species are enriched for loss-of-function intolerant genes; but are depleted for expression quantitative trait loci and cardiovascular-related genes. Our results indicate that response to hypoxic stress is highly conserved in humans and chimpanzees.

Keywords: cardiomyocytes; chimpanzee; evolutionary biology; human; hypoxia; iPSCs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • Hypoxia*
  • Induced Pluripotent Stem Cells / physiology*
  • Myocytes, Cardiac / physiology*
  • Pan troglodytes
  • Stress, Physiological*

Associated data

  • GEO/GSE117192