A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees
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.
Sequencing data have been deposited in GEO under accession code GSE117192
Inter-species differences in response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzeesNCBI Gene Expression Omnibus, GSE117192.
GTEx v7Genotype-Tissue Expression Project.
Loss of function intolerant geneshttps://doi.org/10.1038/nature19057.
BHF-UCL gene association fileBHF-UCL gene association file.
Article and author information
National Heart, Lung, and Blood Institute (HL092206)
- Yoav Gilad
EMBO Long-Term Fellowship (ALTF 751-2014)
- Michelle C Ward
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Sushmita Roy, University of Wisconsin--Madison, United States
- Received: October 23, 2018
- Accepted: April 7, 2019
- Accepted Manuscript published: April 8, 2019 (version 1)
- Version of Record published: May 28, 2019 (version 2)
© 2019, Ward & Gilad
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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