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  The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis

Di Stefano, B., Luo, E.-C., Haggerty, C., Aigner, S., Charlton, J., Brumbaugh, J., et al. (2019). The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis. Cell Stem Cell, 25(5): e13, pp. 622-638. doi:10.1016/j.stem.2019.08.018.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-7950-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-7951-8
Genre: Journal Article

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 Creators:
Di Stefano, Bruno, Author
Luo, En-Ching, Author
Haggerty, Chuck1, Author              
Aigner, Stefan, Author
Charlton, Jocelyn1, Author              
Brumbaugh, Justin, Author
Ji, Fei, Author
Rabano Jiménez, Inés, Author
Clowers, Katie J., Author
Huebner, Aaron J., Author
Clement, Kendell , Author
Lipchina, Inna , Author
de Kort, Marit A. C. , Author
Anselmo, Anthony , Author
Pulice, John , Author
Gerli, Mattia F. M. , Author
Gu, Hongcang , Author
Gygi, Steven P. , Author
Sadreyev, Ruslan I. , Author
Meissner, Alexander1, 2, 3, Author              
Yeo, Gene W. , AuthorHochedlinger, Konrad , Author more..
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              
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA, ou_persistent22              

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Free keywords: embryonic stem cells adult progenitor cells exit from pluripotency self-renewal differentiation P-body RNA helicase DDX6 post-transcriptional regulation naive pluripotency primed pluripotency chromatin
 Abstract: Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, “hyper-pluripotent” state, which readily reprograms to a naive state resembling the preimplantation embryo. We further demonstrate that DDX6 plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner. Mechanistically, DDX6 mediates the translational suppression of target mRNAs in P-bodies. Upon loss of DDX6 activity, P-bodies dissolve and release mRNAs encoding fate-instructive transcription and chromatin factors that re-enter the ribosome pool. Increased translation of these targets impacts cell fate by rewiring the enhancer, heterochromatin, and DNA methylation landscapes of undifferentiated cell types. Collectively, our data establish a link between P-body homeostasis, chromatin organization, and stem cell potency.

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Language(s): eng - English
 Dates: 2019-08-292019-10-032019-11-07
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.stem.2019.08.018
 Degree: -

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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: 25 (5) Sequence Number: e13 Start / End Page: 622 - 638 Identifier: ISSN: 1934-5909
CoNE: https://pure.mpg.de/cone/journals/resource/1934-5909