Journal article

Signalling pathways drive heterogeneity of ground state pluripotency

Kirsten McEwen, Sarah Linnett, Harry Leitch, Prashant Srivastava, Lara Al-Zouabi, Tien-Chi Huang, Maxime Rotival, Alessandro Sardini, Thalia Chan, Sarah Filippi, Michael PH Stumpf, Enrico Petretto, Petra Hajkova

Published : 2018

Abstract

Abstract Pluripotent stem cells (PSCs) can self-renew indefinitely while maintaining the ability to generate all cell types of the body. This plasticity is proposed to require heterogeneity in gene expression, driving a metastable state which may allow flexible cell fate choices. Contrary to this, naive PSC grown in fully defined ‘2i’ environmental conditions, containing small molecule inhibitors of MEK and GSK3 kinases, show homogenous pluripotency and lineage marker expression. However, here we show that 2i induces greater genome-wide heterogeneity than traditional serum-containing growth environments at the population level across both male and female PSCs. This heterogeneity is dynamic a..

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University of Melbourne Researchers

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