Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors
Pluripotent cells can be derived from different types of somatic cells by nuclear reprogramming through the ectopic expression of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc. However, it is unclear whether postmitotic neurons are susceptible to direct reprogramming. Here, we show that...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Wiley Blackwell (John Wiley & Sons)
2012
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| Online Access: | http://hdl.handle.net/1721.1/73480 |
| _version_ | 1811075844596039680 |
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| author | Kim, Jongpil Lengner, Christopher J. Kirak, Oktay Hanna, Jacob Cassady, John P. Lodato, Michael Anthony Wu, Su Faddah, Dina A. Steine, Eveline J. Gao, Qing Fu, DongDong Dawlaty, Meelad M. Jaenisch, Rudolf |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kim, Jongpil Lengner, Christopher J. Kirak, Oktay Hanna, Jacob Cassady, John P. Lodato, Michael Anthony Wu, Su Faddah, Dina A. Steine, Eveline J. Gao, Qing Fu, DongDong Dawlaty, Meelad M. Jaenisch, Rudolf |
| author_sort | Kim, Jongpil |
| collection | MIT |
| description | Pluripotent cells can be derived from different types of somatic cells by nuclear reprogramming through the ectopic expression of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc. However, it is unclear whether postmitotic neurons are susceptible to direct reprogramming. Here, we show that postnatal cortical neurons, the vast majority of which are postmitotic, are amenable to epigenetic reprogramming. However, ectopic expression of the four canonical reprogramming factors is not sufficient to reprogram postnatal neurons. Efficient reprogramming was only achieved after forced cell proliferation by p53 suppression. Additionally, overexpression of repressor element-1 silencing transcription, a suppressor of neuronal gene activity, increased reprogramming efficiencies in combination with the reprogramming factors. Our findings indicate that terminally differentiated postnatal neurons are able to acquire the pluripotent state by direct epigenetic reprogramming, and this process is made more efficient through the suppression of lineage specific gene expression. STEM CELLS 2011;29:992–1000 |
| first_indexed | 2024-09-23T10:12:21Z |
| format | Article |
| id | mit-1721.1/73480 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:12:21Z |
| publishDate | 2012 |
| publisher | Wiley Blackwell (John Wiley & Sons) |
| record_format | dspace |
| spelling | mit-1721.1/734802022-09-30T19:36:32Z Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors Kim, Jongpil Lengner, Christopher J. Kirak, Oktay Hanna, Jacob Cassady, John P. Lodato, Michael Anthony Wu, Su Faddah, Dina A. Steine, Eveline J. Gao, Qing Fu, DongDong Dawlaty, Meelad M. Jaenisch, Rudolf Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. School of Science McGovern Institute for Brain Research at MIT Cassady, John P. Lodato, Michael Anthony Wu, Su Faddah, Dina A. Jaenisch, Rudolf Pluripotent cells can be derived from different types of somatic cells by nuclear reprogramming through the ectopic expression of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc. However, it is unclear whether postmitotic neurons are susceptible to direct reprogramming. Here, we show that postnatal cortical neurons, the vast majority of which are postmitotic, are amenable to epigenetic reprogramming. However, ectopic expression of the four canonical reprogramming factors is not sufficient to reprogram postnatal neurons. Efficient reprogramming was only achieved after forced cell proliferation by p53 suppression. Additionally, overexpression of repressor element-1 silencing transcription, a suppressor of neuronal gene activity, increased reprogramming efficiencies in combination with the reprogramming factors. Our findings indicate that terminally differentiated postnatal neurons are able to acquire the pluripotent state by direct epigenetic reprogramming, and this process is made more efficient through the suppression of lineage specific gene expression. STEM CELLS 2011;29:992–1000 National Institutes of Health (U.S.) (Grant NIH HD045022) National Institutes of Health (U.S.) (Grant 5R37CA084198) Howard Hughes Medical Institute 2012-09-28T17:01:41Z 2012-09-28T17:01:41Z 2011-05 Article http://purl.org/eprint/type/JournalArticle 1066-5099 1549-4918 http://hdl.handle.net/1721.1/73480 Kim, Jongpil et al. “Reprogramming of Postnatal Neurons into Induced Pluripotent Stem Cells by Defined Factors.” STEM CELLS 29.6 (2011): 992–1000. en_US http://dx.doi.org/10.1002/stem.641 Stem Cells Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Wiley Blackwell (John Wiley & Sons) PMC |
| spellingShingle | Kim, Jongpil Lengner, Christopher J. Kirak, Oktay Hanna, Jacob Cassady, John P. Lodato, Michael Anthony Wu, Su Faddah, Dina A. Steine, Eveline J. Gao, Qing Fu, DongDong Dawlaty, Meelad M. Jaenisch, Rudolf Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors |
| title | Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors |
| title_full | Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors |
| title_fullStr | Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors |
| title_full_unstemmed | Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors |
| title_short | Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors |
| title_sort | reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors |
| url | http://hdl.handle.net/1721.1/73480 |
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