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.
- Yoav Gilad
- 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)
© 2019, Ward & Gilad
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