Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency
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 huma...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96520 https://orcid.org/0000-0002-2171-9394 https://orcid.org/0000-0001-8855-8647 |
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| author | Theunissen, Thorold W. Powell, Benjamin E. Wang, Haoyi Mitalipova, Maya Faddah, Dina A. Reddy, Jessica Fan, Zi Peng Maetzel, Dorothea Ganz, Kibibi Shi, Linyu Lungjangwa, Tenzin Imsoonthornruksa, Sumeth Stelzer, Yonatan Rangarajan, Sudharshan D’Alessio, Ana C. Zhang, Jianming Gao, Qing Dawlaty, Meelad M. Young, Richard A. Gray, Nathanael S. Jaenisch, Rudolf Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Theunissen, Thorold W. Powell, Benjamin E. Wang, Haoyi Mitalipova, Maya Faddah, Dina A. Reddy, Jessica Fan, Zi Peng Maetzel, Dorothea Ganz, Kibibi Shi, Linyu Lungjangwa, Tenzin Imsoonthornruksa, Sumeth Stelzer, Yonatan Rangarajan, Sudharshan D’Alessio, Ana C. Zhang, Jianming Gao, Qing Dawlaty, Meelad M. Young, Richard A. Gray, Nathanael S. Jaenisch, Rudolf Young, Richard A. |
| author_sort | Theunissen, Thorold W. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:47:44Z |
| format | Article |
| id | mit-1721.1/96520 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:47:44Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/965202022-10-01T11:09:21Z Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency Theunissen, Thorold W. Powell, Benjamin E. Wang, Haoyi Mitalipova, Maya Faddah, Dina A. Reddy, Jessica Fan, Zi Peng Maetzel, Dorothea Ganz, Kibibi Shi, Linyu Lungjangwa, Tenzin Imsoonthornruksa, Sumeth Stelzer, Yonatan Rangarajan, Sudharshan D’Alessio, Ana C. Zhang, Jianming Gao, Qing Dawlaty, Meelad M. Young, Richard A. Gray, Nathanael S. Jaenisch, Rudolf Young, Richard A. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Faddah, Dina A. Reddy, Jessica Young, Richard A. Jaenisch, Rudolf 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. Simons Foundation (Grant SFLIFE 286977) National Institutes of Health (U.S.) (Grant RO1-CA084198) National Science Foundation (U.S.). Graduate Research Fellowship Jerome and Florence Brill Graduate Student Fellowship 2015-04-10T17:28:40Z 2015-04-10T17:28:40Z 2014-07 2014-06 Article http://purl.org/eprint/type/JournalArticle 19345909 http://hdl.handle.net/1721.1/96520 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. https://orcid.org/0000-0002-2171-9394 https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1016/j.stem.2014.07.002 Cell Stem Cell Creative Commons Attribution Unported License http://creativecommons.org/licenses/by/3.0/ application/pdf Elsevier Elsevier Open Access |
| spellingShingle | Theunissen, Thorold W. Powell, Benjamin E. Wang, Haoyi Mitalipova, Maya Faddah, Dina A. Reddy, Jessica Fan, Zi Peng Maetzel, Dorothea Ganz, Kibibi Shi, Linyu Lungjangwa, Tenzin Imsoonthornruksa, Sumeth Stelzer, Yonatan Rangarajan, Sudharshan D’Alessio, Ana C. Zhang, Jianming Gao, Qing Dawlaty, Meelad M. Young, Richard A. Gray, Nathanael S. Jaenisch, Rudolf Young, Richard A. Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency |
| title | Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency |
| title_full | Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency |
| title_fullStr | Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency |
| title_full_unstemmed | Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency |
| title_short | Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency |
| title_sort | systematic identification of culture conditions for induction and maintenance of naive human pluripotency |
| url | http://hdl.handle.net/1721.1/96520 https://orcid.org/0000-0002-2171-9394 https://orcid.org/0000-0001-8855-8647 |
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