1. Evolutionary Biology
Download icon

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
Research Article
  • Cited 0
  • Views 731
  • Annotations
Cite this article as: eLife 2019;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.

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)

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.

Metrics

  • 731
    Page views
  • 97
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Evolutionary Biology
    2. Genetics and Genomics
    Petar Pajic et al.
    Research Article
    1. Evolutionary Biology
    Marco Romano et al.
    Research Article