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dc.contributor.authorKim, K.
dc.contributor.authorDoi, A.
dc.contributor.authorWen, B.
dc.contributor.authorNg, K.
dc.contributor.authorZhao, R.
dc.contributor.authorCahan, P.
dc.contributor.authorKim, J.
dc.contributor.authorAryee, M. J.
dc.contributor.authorJi, H.
dc.contributor.authorEhrlich, L.
dc.contributor.authorYabuuchi, A.
dc.contributor.authorTakeuchi, A.
dc.contributor.authorCunniff, K. C.
dc.contributor.authorHongguang, H.
dc.contributor.authorMckinney-Freeman, S.
dc.contributor.authorNaveiras, O.
dc.contributor.authorYoon, T. J.
dc.contributor.authorIrizarry, R. A.
dc.contributor.authorJung, N.
dc.contributor.authorSeita, J.
dc.contributor.authorHanna, J.
dc.contributor.authorMurakami, P.
dc.contributor.authorJaenisch, R.
dc.contributor.authorWeissleder, R.
dc.contributor.authorOrkin, S. H.
dc.contributor.authorWeissman, I. L.
dc.contributor.authorFeinberg, A. P.
dc.contributor.authorDaley, G. Q.
dc.date.accessioned2019-09-21T03:38:03Z
dc.date.issued2010
dc.identifier.citationKim, K., A. Doi, B. Wen, K. Ng, R. Zhao, P. Cahan, J. Kim, et al. 2010. “Epigenetic Memory in Induced Pluripotent Stem Cells.” Nature 467 (7313): 285–90. https://doi.org/10.1038/nature09342.
dc.identifier.issn0028-0836
dc.identifier.issn0302-2889
dc.identifier.issn1476-4687
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384402*
dc.description.abstractSomatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer more readily establishes the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.
dc.language.isoen_US
dc.publisherNature Research (part of Springer Nature)
dash.licenseLAA
dc.titleEpigenetic memory in induced pluripotent stem cells
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalNature
dash.depositing.authorWeissleder, Ralph::ea07ce19f187d4fab47c56ee97fa5c5a::600
dc.date.available2019-09-21T03:38:03Z
dash.workflow.comments1Science Serial ID 72904
dc.identifier.doi10.1038/nature09342
dash.source.volume467;7313


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