Molecular Criteria for Defining the Naive Human Pluripotent State
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Jaenisch_Molecular criteria.pdf
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5.61 MB
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Author(s)
Theunissen, Thorold W.
Friedli, Marc
He, Yupeng
Planet, Evarist
O’Neil, Ryan C.
Markoulaki, Styliani
Pontis, Julien
Wang, Haoyi
Iouranova, Alexandra
Imbeault, Michaël
Date Issued
July 2016
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Theunissen, Thorold W.; Friedli, Marc; He, Yupeng; Planet, Evarist; O’Neil, Ryan C.; Markoulaki, Styliani; Pontis, Julien et al. “Molecular Criteria for Defining the Naive Human Pluripotent State.” Cell Stem Cell 19, no. 4 (October 2016): 502–515. © 2016 The Authors
Version
Final published version
Abstract
Recent studies have aimed to convert cultured human pluripotent cells to a naive state, but it remains unclear to what extent the resulting cells recapitulate in vivo naive pluripotency. Here we propose a set of molecular criteria for evaluating the naive human pluripotent state by comparing it to the human embryo. We show that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. We also show that induction of the naive state is accompanied by genome-wide DNA hypomethylation, which is reversible except at imprinted genes, and that the X chromosome status resembles that of the human preimplantation embryo. However, we did not see efficient incorporation of naive human cells into mouse embryos. Overall, the different naive conditions we tested showed varied relationships to human embryonic states based on molecular criteria, providing a backdrop for future analysis of naive human pluripotency.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1016/j.stem.2016.06.011
