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

  1. Michelle C Ward  Is a corresponding author
  2. Yoav Gilad  Is a corresponding author
  1. University of Chicago, United States

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.

Data availability

Sequencing data have been deposited in GEO under accession code GSE117192

The following data sets were generated
The following previously published data sets were used
    1. GTEx consortium
    (2018) GTEx v7
    Genotype-Tissue Expression Project.

Article and author information

Author details

  1. Michelle C Ward

    Department of Medicine, University of Chicago, Chicago, United States
    For correspondence
    mcward@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1485-320X
  2. Yoav Gilad

    Department of Medicine, University of Chicago, Chicago, United States
    For correspondence
    gilad@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8284-8926

Funding

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.

Reviewing Editor

  1. Sushmita Roy, University of Wisconsin--Madison, United States

Publication history

  1. Received: October 23, 2018
  2. Accepted: April 7, 2019
  3. Accepted Manuscript published: April 8, 2019 (version 1)
  4. Version of Record published: May 28, 2019 (version 2)

Copyright

© 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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  1. Michelle C Ward
  2. Yoav Gilad
(2019)
A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees
eLife 8:e42374.
https://doi.org/10.7554/eLife.42374

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