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The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis.
Di Stefano, Bruno; Luo, En-Ching; Haggerty, Chuck; Aigner, Stefan; Charlton, Jocelyn; Brumbaugh, Justin; Ji, Fei; Rabano Jiménez, Inés; Clowers, Katie J; Huebner, Aaron J; Clement, Kendell; Lipchina, Inna; de Kort, Marit A C; Anselmo, Anthony; Pulice, John; Gerli, Mattia F M; Gu, Hongcang; Gygi, Steven P; Sadreyev, Ruslan I; Meissner, Alexander; Yeo, Gene W; Hochedlinger, Konrad.
Afiliação
  • Di Stefano B; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA
  • Luo EC; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
  • Haggerty C; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
  • Aigner S; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
  • Charlton J; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
  • Brumbaugh J; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA
  • Ji F; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
  • Rabano Jiménez I; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
  • Clowers KJ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Huebner AJ; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA
  • Clement K; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lipchina I; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA
  • de Kort MAC; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA
  • Anselmo A; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
  • Pulice J; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA
  • Gerli MFM; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
  • Gu H; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gygi SP; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Sadreyev RI; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
  • Meissner A; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Yeo GW; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic addre
  • Hochedlinger K; Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA
Cell Stem Cell ; 25(5): 622-638.e13, 2019 11 07.
Article em En | MEDLINE | ID: mdl-31588046
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleoproteínas / Diferenciação Celular / Proteínas Proto-Oncogênicas / RNA Helicases DEAD-box / Células-Tronco Pluripotentes Induzidas / Plasticidade Celular Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleoproteínas / Diferenciação Celular / Proteínas Proto-Oncogênicas / RNA Helicases DEAD-box / Células-Tronco Pluripotentes Induzidas / Plasticidade Celular Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article