Human embryonic stem cells with biological and epigenetic to those of mouse ESCs
Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewi...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2011
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| Online Access: | http://hdl.handle.net/1721.1/61398 |
| _version_ | 1826190023855177728 |
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| author | Jaenisch, Rudolf Hanna, Jacob Cheng, Albert W. Saha, Krishanu Kim, Jongpil Lengner, Christopher J. Soldner, Frank Cassady, John P. Muffat, Julien Carey, Bryce W. |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Jaenisch, Rudolf Hanna, Jacob Cheng, Albert W. Saha, Krishanu Kim, Jongpil Lengner, Christopher J. Soldner, Frank Cassady, John P. Muffat, Julien Carey, Bryce W. |
| author_sort | Jaenisch, Rudolf |
| collection | MIT |
| description | Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated “naïve” human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research. |
| first_indexed | 2024-09-23T08:33:51Z |
| format | Article |
| id | mit-1721.1/61398 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:33:51Z |
| publishDate | 2011 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/613982022-09-23T12:56:12Z Human embryonic stem cells with biological and epigenetic to those of mouse ESCs Jaenisch, Rudolf Hanna, Jacob Cheng, Albert W. Saha, Krishanu Kim, Jongpil Lengner, Christopher J. Soldner, Frank Cassady, John P. Muffat, Julien Carey, Bryce W. Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Jaenisch, Rudolf Jaenisch, Rudolf Saha, Krishanu Cheng, Albert W. Hanna, Jacob Kim, Jongpil Lengner, Christopher J. Soldner, Frank Cassady, John P. Muffat, Julien Carey, Bryce W. Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated “naïve” human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research. Genzyme Corporation Helen Hay Whitney Foundation Society in Science – The Branco Weiss Fellowship Croucher Foundation 2011-03-03T22:28:46Z 2011-03-03T22:28:46Z 2010-05 2010-04 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/61398 Hanna, Jacob, et al. "Human embryonic stem cells with biological and epigenetic to those of mouse ESCs." PNAS May 18, 2010 vol. 107 no. 20 9222-9227.©2010 by the National Academy of Sciences. en_US http://dx.doi.org/10.1073/pnas.1004584107 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Jaenisch, Rudolf Hanna, Jacob Cheng, Albert W. Saha, Krishanu Kim, Jongpil Lengner, Christopher J. Soldner, Frank Cassady, John P. Muffat, Julien Carey, Bryce W. Human embryonic stem cells with biological and epigenetic to those of mouse ESCs |
| title | Human embryonic stem cells with biological and epigenetic to those of mouse ESCs |
| title_full | Human embryonic stem cells with biological and epigenetic to those of mouse ESCs |
| title_fullStr | Human embryonic stem cells with biological and epigenetic to those of mouse ESCs |
| title_full_unstemmed | Human embryonic stem cells with biological and epigenetic to those of mouse ESCs |
| title_short | Human embryonic stem cells with biological and epigenetic to those of mouse ESCs |
| title_sort | human embryonic stem cells with biological and epigenetic to those of mouse escs |
| url | http://hdl.handle.net/1721.1/61398 |
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