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dc.contributor.authorBuganim, Yosef
dc.contributor.authorMarkoulaki, Styliani
dc.contributor.authorvan Wietmarschen, Niek
dc.contributor.authorWu, Tao
dc.contributor.authorGanz, Kibibi
dc.contributor.authorAkhtar-Zaidi, Batool
dc.contributor.authorHe, Yupeng
dc.contributor.authorAbraham, Brian J.
dc.contributor.authorPorubsky, David
dc.contributor.authorKulenkampff, Elisabeth
dc.contributor.authorShi, Linyu
dc.contributor.authorGao, Qing
dc.contributor.authorSarkar, Sovan
dc.contributor.authorCohen, Malkiel
dc.contributor.authorGoldmann, Johanna
dc.contributor.authorNery, Joseph R.
dc.contributor.authorSchultz, Matthew D.
dc.contributor.authorEcker, Joseph R.
dc.contributor.authorXiao, Andrew
dc.contributor.authorLansdorp, Peter M.
dc.contributor.authorHoke, Heather Ashley
dc.contributor.authorJaenisch, Rudolf
dc.contributor.authorFaddah, Dina A.
dc.contributor.authorYoung, Richard A.
dc.date.accessioned2017-06-01T17:32:52Z
dc.date.available2017-06-01T17:32:52Z
dc.date.issued2014-09
dc.date.submitted2014-03
dc.identifier.issn1934-5909
dc.identifier.urihttp://hdl.handle.net/1721.1/109508
dc.description.abstractInduced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliably high-quality iPSCs will be needed for future therapeutic applications. Here, we show that one major determinant of iPSC quality is the combination of reprogramming factors used. Based on tetraploid complementation, we found that ectopic expression of Sall4, Nanog, Esrrb, and Lin28 (SNEL) in mouse embryonic fibroblasts (MEFs) generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. Although differentially methylated regions, transcript number of master regulators, establishment of specific superenhancers, and global aneuploidy were comparable between high- and low-quality lines, aberrant gene expression, trisomy of chromosome 8, and abnormal H2A.X deposition were distinguishing features that could potentially also be applicable to human.en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Graduate Research Fellowship Programen_US
dc.description.sponsorshipWhitehead Institute for Biomedical Research (Jerome and Florence Brill Graduate Student Fellowship)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grants HD 045022)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (R37CA084198)en_US
dc.description.sponsorshipGordon and Betty Moore Foundation (GMBF3034)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.stem.2014.07.003en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleThe Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selectionen_US
dc.typeArticleen_US
dc.identifier.citationBuganim, Yosef, Styliani Markoulaki, Niek van Wietmarschen, Heather Hoke, Tao Wu, Kibibi Ganz, Batool Akhtar-Zaidi, et al. “The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection.” Cell Stem Cell 15, no. 3 (September 2014): 295–309. © 2014 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorHoke, Heather Ashley
dc.contributor.mitauthorFaddah, Dina Adel
dc.contributor.mitauthorYoung, Richard A
dc.contributor.mitauthorJaenisch, Rudolf
dc.relation.journalCell Stem Cellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsBuganim, Yosef; Markoulaki, Styliani; van Wietmarschen, Niek; Hoke, Heather; Wu, Tao; Ganz, Kibibi; Akhtar-Zaidi, Batool; He, Yupeng; Abraham, Brian J.; Porubsky, David; Kulenkampff, Elisabeth; Faddah, Dina A.; Shi, Linyu; Gao, Qing; Sarkar, Sovan; Cohen, Malkiel; Goldmann, Johanna; Nery, Joseph R.; Schultz, Matthew D.; Ecker, Joseph R.; Xiao, Andrew; Young, Richard A.; Lansdorp, Peter M.; Jaenisch, Rudolfen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-8855-8647
mit.licensePUBLISHER_CCen_US


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