Show simple item record

dc.contributor.authorJaenisch, Rudolf
dc.contributor.authorLengner, Christopher J.
dc.contributor.authorvan Oudenaarden, Alexander
dc.contributor.authorVan Zon, Jeroen Sebastiaan
dc.contributor.authorPando, Bernardo Fabian
dc.contributor.authorSaha, Krishanu
dc.contributor.authorHanna, Jacob
dc.contributor.authorCreyghton, Menno P.
dc.date.accessioned2010-09-07T19:56:43Z
dc.date.available2010-09-07T19:56:43Z
dc.date.issued2009-12
dc.identifier.issn1476-4687
dc.identifier.issn0028-0836
dc.identifier.urihttp://hdl.handle.net/1721.1/58480
dc.description.abstractDirect 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.en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nature08592en_US
dc.rightsArticle 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.en_US
dc.sourceRudolf Jaenischen_US
dc.titleDirect cell reprogramming is a stochastic process amenable to accelerationen_US
dc.typeArticleen_US
dc.identifier.citationHanna, 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
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.approverJaenisch, Rudolf
dc.contributor.mitauthorJaenisch, Rudolf
dc.contributor.mitauthorLengner, Christopher J.
dc.contributor.mitauthorvan Oudenaarden, Alexander
dc.contributor.mitauthorVan Zon, Jeroen Sebastiaan
dc.contributor.mitauthorPando, Bernardo Fabian
dc.relation.journalNatureen_US
dc.eprint.versionAuthor's final manuscript
dc.type.urihttp://purl.org/eprint/type/SubmittedJournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHanna, Jacob; Saha, Krishanu; Pando, Bernardo; van Zon, Jeroen; Lengner, Christopher J.; Creyghton, Menno P.; van Oudenaarden, Alexander; Jaenisch, Rudolfen
mit.licensePUBLISHER_POLICYen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record