Direct cell reprogramming is a stochastic process amenable to acceleration
Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming is a conti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2010
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| Online Access: | http://hdl.handle.net/1721.1/58480 |
| _version_ | 1811095953287938048 |
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| author | Jaenisch, Rudolf Lengner, Christopher J. van Oudenaarden, Alexander Van Zon, Jeroen Sebastiaan Pando, Bernardo Fabian Saha, Krishanu Hanna, Jacob Creyghton, Menno P. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Jaenisch, Rudolf Lengner, Christopher J. van Oudenaarden, Alexander Van Zon, Jeroen Sebastiaan Pando, Bernardo Fabian Saha, Krishanu Hanna, Jacob Creyghton, Menno P. |
| author_sort | Jaenisch, Rudolf |
| collection | MIT |
| description | Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) can be
achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that
reprogramming is a continuous stochastic process where almost all donor cells eventually give rise to iPSCs upon continued growth and transcription factor expression. Additional inhibition the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPSC formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell division rate independent manner. Quantitative analyses define distinct cell division rate dependent and independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency. |
| first_indexed | 2024-09-23T16:35:38Z |
| format | Article |
| id | mit-1721.1/58480 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:35:38Z |
| publishDate | 2010 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/584802022-10-02T08:20:03Z Direct cell reprogramming is a stochastic process amenable to acceleration Jaenisch, Rudolf Lengner, Christopher J. van Oudenaarden, Alexander Van Zon, Jeroen Sebastiaan Pando, Bernardo Fabian Saha, Krishanu Hanna, Jacob Creyghton, Menno P. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Physics Jaenisch, Rudolf Jaenisch, Rudolf Lengner, Christopher J. van Oudenaarden, Alexander Van Zon, Jeroen Sebastiaan Pando, Bernardo Fabian Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming is a continuous stochastic process where almost all donor cells eventually give rise to iPSCs upon continued growth and transcription factor expression. Additional inhibition the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPSC formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell division rate independent manner. Quantitative analyses define distinct cell division rate dependent and independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency. 2010-09-07T19:56:43Z 2010-09-07T19:56:43Z 2009-12 Article http://purl.org/eprint/type/SubmittedJournalArticle 1476-4687 0028-0836 http://hdl.handle.net/1721.1/58480 Hanna, Jacob et al. “Direct cell reprogramming is a stochastic process amenable to acceleration.” Nature 462.7273 (2009): 595-601. © 2009 Nature Publishing Group. en_US http://dx.doi.org/10.1038/nature08592 Nature 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 Nature Publishing Group Rudolf Jaenisch |
| spellingShingle | Jaenisch, Rudolf Lengner, Christopher J. van Oudenaarden, Alexander Van Zon, Jeroen Sebastiaan Pando, Bernardo Fabian Saha, Krishanu Hanna, Jacob Creyghton, Menno P. Direct cell reprogramming is a stochastic process amenable to acceleration |
| title | Direct cell reprogramming is a stochastic process amenable to acceleration |
| title_full | Direct cell reprogramming is a stochastic process amenable to acceleration |
| title_fullStr | Direct cell reprogramming is a stochastic process amenable to acceleration |
| title_full_unstemmed | Direct cell reprogramming is a stochastic process amenable to acceleration |
| title_short | Direct cell reprogramming is a stochastic process amenable to acceleration |
| title_sort | direct cell reprogramming is a stochastic process amenable to acceleration |
| url | http://hdl.handle.net/1721.1/58480 |
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