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

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 H. Naik, Daniela Zalcenstein, Othmar Korn, Shian Su, Irene Gallego Romero, Catrina Spruce, Christopher L. Baker, Tracy C. McGarr, Christine A. Wells and Martin F. Pera ()
Additional contact information
Kevin X. Lau: University of Melbourne
Elizabeth A. Mason: 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
Andrew Keniry: The Walter and Eliza Hall Institute
Tamara Beck: The Walter and Eliza Hall Institute
Marnie E. Blewitt: The Walter and Eliza Hall Institute
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
Martin F. Pera: University of Melbourne

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16214-8

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