Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency
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Jaenisch_Systematic identification.pdf
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Author(s)
Theunissen, Thorold W.
Powell, Benjamin E.
Wang, Haoyi
Mitalipova, Maya
Faddah, Dina A.
Reddy, Jessica
Fan, Zi Peng
Maetzel, Dorothea
Ganz, Kibibi
Shi, Linyu
Date Issued
July 2014
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Theunissen, Thorold W., Benjamin E. Powell, Haoyi Wang, Maya Mitalipova, Dina A. Faddah, Jessica Reddy, Zi Peng Fan, et al. “Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency.” Cell Stem Cell 15, no. 4 (October 2014): 471–487.
Version
Final published version
Abstract
Embryonic stem cells (ESCs) of mice and humans have distinct molecular and biological characteristics, raising the question of whether an earlier, “naive” state of pluripotency may exist in humans. Here we took a systematic approach to identify small molecules that support self-renewal of naive human ESCs based on maintenance of endogenous OCT4 distal enhancer activity, a molecular signature of ground state pluripotency. Iterative chemical screening identified a combination of five kinase inhibitors that induces and maintains OCT4 distal enhancer activity when applied directly to conventional human ESCs. These inhibitors generate human pluripotent cells in which transcription factors associated with the ground state of pluripotency are highly upregulated and bivalent chromatin domains are depleted. Comparison with previously reported naive human ESCs indicates that our conditions capture a distinct pluripotent state in humans that closely resembles that of mouse ESCs. This study presents a framework for defining the culture requirements of naive human pluripotent cells.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution Unported License
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DOI of Published Version
https://doi.org/10.1016/j.stem.2014.07.002
