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Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal

Author

Listed:
  • Kevin X. Lau

    (University of Melbourne)

  • Elizabeth A. Mason

    (University of Melbourne
    University of Melbourne)

  • Joshua Kie

    (University of Melbourne)

  • David P. Souza

    (University of Melbourne)

  • Joachim Kloehn

    (University of Melbourne)

  • Dedreia Tull

    (University of Melbourne)

  • Malcolm J. McConville

    (University of Melbourne
    University of Melbourne)

  • Andrew Keniry

    (The Walter and Eliza Hall Institute
    University of Melbourne)

  • Tamara Beck

    (The Walter and Eliza Hall Institute)

  • Marnie E. Blewitt

    (The Walter and Eliza Hall Institute
    University of Melbourne)

  • Matthew E. Ritchie

    (The Walter and Eliza Hall Institute)

  • Shalin H. Naik

    (The Walter and Eliza Hall Institute)

  • Daniela Zalcenstein

    (The Walter and Eliza Hall Institute)

  • Othmar Korn

    (The University of Queensland)

  • Shian Su

    (The Walter and Eliza Hall Institute)

  • Irene Gallego Romero

    (University of Melbourne)

  • Catrina Spruce

    (The Jackson Laboratory)

  • Christopher L. Baker

    (The Jackson Laboratory)

  • Tracy C. McGarr

    (The Jackson Laboratory)

  • Christine A. Wells

    (University of Melbourne
    University of Melbourne
    The Walter and Eliza Hall Institute)

  • Martin F. Pera

    (University of Melbourne
    The Walter and Eliza Hall Institute
    The Jackson Laboratory
    The Florey Institute of Neuroscience and Mental Health)

Abstract

Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation stage of embryogenesis. Heterogeneity within hPSC cultures complicates this interspecies comparison. Here we show that a subpopulation of archetypal hPSC enriched for high self-renewal capacity (ESR) has distinct properties relative to the bulk of the population, including a cell cycle with a very low G1 fraction and a metabolomic profile that reflects a combination of oxidative phosphorylation and glycolysis. ESR cells are pluripotent and capable of differentiation into primordial germ cell-like cells. Global DNA methylation levels in the ESR subpopulation are lower than those in mouse epiblast stem cells. Chromatin accessibility analysis revealed a unique set of open chromatin sites in ESR cells. RNA-seq at the subpopulation and single cell levels shows that, unlike mouse epiblast stem cells, the ESR subset of hPSC displays no lineage priming, and that it can be clearly distinguished from gastrulating and extraembryonic cell populations in the primate embryo. ESR hPSC correspond to an earlier stage of post-implantation development than mouse epiblast stem cells.

Suggested Citation

  • Kevin X. Lau & Elizabeth A. Mason & Joshua Kie & David P. Souza & Joachim Kloehn & Dedreia Tull & Malcolm J. McConville & Andrew Keniry & Tamara Beck & Marnie E. Blewitt & Matthew E. Ritchie & Shalin , 2020. "Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16214-8
    DOI: 10.1038/s41467-020-16214-8
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    Cited by:

    1. Timothy D. Arthur & Jennifer P. Nguyen & Agnieszka D’Antonio-Chronowska & Hiroko Matsui & Nayara S. Silva & Isaac N. Joshua & André D. Luchessi & William W. Young Greenwald & Matteo D’Antonio & Martin, 2024. "Complex regulatory networks influence pluripotent cell state transitions in human iPSCs," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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