@article{907803ae01224423802d35a509464dd8,
title = "Molecular Criteria for Defining the Naive Human Pluripotent State",
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.",
keywords = "DNA methylation, X chromosome reactivation, embryonic stem cells, imprinting, mouse-human chimeras, pluripotency, transposable elements",
author = "Theunissen, {Thorold W.} and Marc Friedli and Yupeng He and Evarist Planet and O'Neil, {Ryan C.} and Styliani Markoulaki and Julien Pontis and Haoyi Wang and Alexandra Iouranova and Micha{\"e}l Imbeault and Julien Duc and Cohen, {Malkiel A.} and Wert, {Katherine J.} and Rosa Castanon and Zhuzhu Zhang and Yanmei Huang and Nery, {Joseph R.} and Jesse Drotar and Tenzin Lungjangwa and Didier Trono and Ecker, {Joseph R.} and Rudolf Jaenisch",
note = "Funding Information: We thank Ruth Flannery for embryo processing, Patti Wisniewski and Colin Zollo for cell sorting, the University of Lausanne Genomic core facility for sequencing, and Dr. Jacob Hanna (Weizmann Institute) for sharing cells. This study was supported by grants from the Simons Foundation (SFLIFE #286977 to R.J.) and in part by the NIH (RO1-CA084198) to R.J., and from the Swiss National Science Foundation and the European Research Council (KRABnKAP, No. 268721) to D.T. The work in the J.R.E. laboratory was supported by the Howard Hughes Medical Institute and Gordon and Betty Moore Foundation (GBMF3034) and the Mary K. Chapman Foundation. J.R.E. is an Investigator of the Howard Hughes Medical Institute. T.W.T. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (098889/Z/12/Z), J.P. by a Foundation Bettencourt Award and by the Association pour la Recherche sur le Cancer (ARC), and M.I. by a postdoctoral training grant from the Fonds de la Recherche en Sant{\'e} du Qu{\'e}bec. R.J. is co-founder of Fate Therapeutics and an adviser to Stemgent. Publisher Copyright: {\textcopyright} 2016 The Authors",
year = "2016",
month = oct,
day = "6",
doi = "10.1016/j.stem.2016.06.011",
language = "English (US)",
volume = "19",
pages = "502--515",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}