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  Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming

Schwarz, B. A., Cetinbas, M., Clement, K., Walsh, R. M., Cheloufi, S., Gu, H., et al. (2018). Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming. Cell Stem Cell, 23(2): e5, pp. 289-305. doi:10.1016/j.stem.2018.06.013.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-4C5E-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-4C5F-F
Genre: Journal Article

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 Creators:
Schwarz, Benjamin A. , Author
Cetinbas, Murat , Author
Clement, Kendell , Author
Walsh, Ryan M. , Author
Cheloufi, Sihem , Author
Gu, Hongcang , Author
Langkabel, Jan , Author
Kamiya, Akihide , Author
Schorle, Hubert, Author
Meissner, Alexander1, 2, 3, 4, Author              
Sadreyev, Ruslan I. , Author
Hochedlinger, Konrad , Author
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA, ou_persistent22              
3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA, ou_persistent22              
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA, ou_persistent22              

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Free keywords: DNA methylation; cell surface antigens; cellular reprogramming; chromatin; epigenomics; gene expression; induced pluripotent stem cells; transcription factors
 Abstract: Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is typically very inefficient, complicating mechanistic studies. We identified and molecularly characterized rare, early intermediates poised to reprogram with up to 95% efficiency, without perturbing additional genes or pathways, during iPSC generation from mouse embryonic fibroblasts. Analysis of these cells uncovered transcription factors (e.g., Tfap2c and Bex2) that are important for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed an early wave of DNA demethylation that is uncoupled from de novo methylation of somatic regions late in reprogramming. Our study underscores the importance of investigating rare intermediates poised to produce iPSCs, provides insights into reprogramming mechanisms, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change.

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Language(s): eng - English
 Dates: 2018-06-152018-07-122018-08-02
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.stem.2018.06.013
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Title: Cell Stem Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: 17 Volume / Issue: 23 (2) Sequence Number: e5 Start / End Page: 289 - 305 Identifier: ISSN: 1934-5909
CoNE: https://pure.mpg.de/cone/journals/resource/1934-5909