@article{09a3f52e2403410981455cc74fbea41f,
title = "Systematic identification of culture conditions for induction and maintenance of naive human pluripotency",
abstract = "Embryonic stem cells (ESCs) of mice and humans have distinctmolecular and biological characteristics, raising thequestionofwhetheranearlier, {"}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, amolecular 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 associatedwith 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 ofmouse ESCs. This study presents a framework for defining the culture requirements of naive human pluripotent cells.",
author = "Theunissen, {Thorold W.} and Powell, {Benjamin E.} and Haoyi Wang and Maya Mitalipova and Faddah, {Dina A.} and Jessica Reddy and Fan, {Zi Peng} and Dorothea Maetzel and Kibibi Ganz and Linyu Shi and Tenzin Lungjangwa and Sumeth Imsoonthornruksa and Yonatan Stelzer and Sudharshan Rangarajan and Ana D'Alessio and Jianming Zhang and Qing Gao and Dawlaty, {Meelad M.} and Young, {Richard A.} and Gray, {Nathanael S.} and Rudolf Jaenisch",
note = "Funding Information: We thank Dongdong Fu for sectioning, Raaji Alagappan and Ping Xu for preparation of MEFs, Ruth Flannery for embryo processing, Patti Wisniewski and Colin Zollo for cell sorting, David Sabatini and Kathleen Ottina for use of the Zymark Liquid Handling system, the Whitehead Genome Technology Core for assistance with expression array and ChIP-Seq analysis, and Jacob Hanna (Weizmann Institute) for providing C1-AAVS1-GFP human ESCs. This study was supported by a grant from the Simons Foundation (SFLIFE #286977 to R.J) and was supported in part by NIH grant RO1-CA084198 to R.J. T.W.T. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (098889/Z/12/Z). B.E.P. is supported by a Boehringer Ingelheim Fonds Ph.D. Fellowship and a Jerome and Florence Brill Graduate Student Fellowship. D.A.F. is supported by a National Science Foundation Graduate Research Fellowship and a Jerome and Florence Brill Graduate Student Fellowship. Y.S. is supported by a Human Frontier Science Program Postdoctoral Fellowship. R.J. is a cofounder of Fate Therapeutics and an adviser to Stemgent. Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",
year = "2014",
doi = "10.1016/j.stem.2014.07.002",
language = "English",
volume = "15",
pages = "471--487",
journal = "Cell Stem Cell",
issn = "1934-5909",
number = "4",
}