Molecular Criteria for Defining the Naive Human Pluripotent State

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 t...

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Main Authors: Theunissen, Thorold W., Friedli, Marc, He, Yupeng, Planet, Evarist, O’Neil, Ryan C., Markoulaki, Styliani, Pontis, Julien, Wang, Haoyi, Iouranova, Alexandra, Imbeault, Michaël, Duc, Julien, Cohen, Malkiel A., Wert, Katherine J., Castanon, Rosa, Zhang, Zhuzhu, Huang, Yanmei, Nery, Joseph R., Drotar, Jesse, Lungjangwa, Tenzin, Trono, Didier, Ecker, Joseph R., Jaenisch, Rudolf
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2017
Online Access:http://hdl.handle.net/1721.1/109074
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author Theunissen, Thorold W.
Friedli, Marc
He, Yupeng
Planet, Evarist
O’Neil, Ryan C.
Markoulaki, Styliani
Pontis, Julien
Wang, Haoyi
Iouranova, Alexandra
Imbeault, Michaël
Duc, Julien
Cohen, Malkiel A.
Wert, Katherine J.
Castanon, Rosa
Zhang, Zhuzhu
Huang, Yanmei
Nery, Joseph R.
Drotar, Jesse
Lungjangwa, Tenzin
Trono, Didier
Ecker, Joseph R.
Jaenisch, Rudolf
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Theunissen, Thorold W.
Friedli, Marc
He, Yupeng
Planet, Evarist
O’Neil, Ryan C.
Markoulaki, Styliani
Pontis, Julien
Wang, Haoyi
Iouranova, Alexandra
Imbeault, Michaël
Duc, Julien
Cohen, Malkiel A.
Wert, Katherine J.
Castanon, Rosa
Zhang, Zhuzhu
Huang, Yanmei
Nery, Joseph R.
Drotar, Jesse
Lungjangwa, Tenzin
Trono, Didier
Ecker, Joseph R.
Jaenisch, Rudolf
author_sort Theunissen, Thorold W.
collection MIT
description 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.
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spelling mit-1721.1/1090742022-10-01T13:24:11Z Molecular Criteria for Defining the Naive Human Pluripotent State Theunissen, Thorold W. Friedli, Marc He, Yupeng Planet, Evarist O’Neil, Ryan C. Markoulaki, Styliani Pontis, Julien Wang, Haoyi Iouranova, Alexandra Imbeault, Michaël Duc, Julien Cohen, Malkiel A. Wert, Katherine J. Castanon, Rosa Zhang, Zhuzhu Huang, Yanmei Nery, Joseph R. Drotar, Jesse Lungjangwa, Tenzin Trono, Didier Ecker, Joseph R. Jaenisch, Rudolf Massachusetts Institute of Technology. Department of Biology Jaenisch, Rudolf 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. Simons Foundation Autism Research Initiative (SFLIFE #286977) United States. National Institutes of Health (RO1-CA084198) 2017-05-15T13:27:01Z 2017-05-15T13:27:01Z 2016-07 2016-04 Article http://purl.org/eprint/type/JournalArticle 1934-5909 http://hdl.handle.net/1721.1/109074 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 en_US http://dx.doi.org/10.1016/j.stem.2016.06.011 Cell Stem Cell Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier Elsevier
spellingShingle Theunissen, Thorold W.
Friedli, Marc
He, Yupeng
Planet, Evarist
O’Neil, Ryan C.
Markoulaki, Styliani
Pontis, Julien
Wang, Haoyi
Iouranova, Alexandra
Imbeault, Michaël
Duc, Julien
Cohen, Malkiel A.
Wert, Katherine J.
Castanon, Rosa
Zhang, Zhuzhu
Huang, Yanmei
Nery, Joseph R.
Drotar, Jesse
Lungjangwa, Tenzin
Trono, Didier
Ecker, Joseph R.
Jaenisch, Rudolf
Molecular Criteria for Defining the Naive Human Pluripotent State
title Molecular Criteria for Defining the Naive Human Pluripotent State
title_full Molecular Criteria for Defining the Naive Human Pluripotent State
title_fullStr Molecular Criteria for Defining the Naive Human Pluripotent State
title_full_unstemmed Molecular Criteria for Defining the Naive Human Pluripotent State
title_short Molecular Criteria for Defining the Naive Human Pluripotent State
title_sort molecular criteria for defining the naive human pluripotent state
url http://hdl.handle.net/1721.1/109074
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