ArticleCell stem cell2019
The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis.
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Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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90citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
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Who cites it
90 citing papers in PubMed, 153 citations in OpenAlex.
- Uncovering essential RNA components of fusion oncoprotein condensates using bicon-seq.The EMBO journal · 2026Article
- Modulating RNA condensates to control cell fate.Nature biotechnology · 2026Article
- Selective RNA sequestration in biomolecular condensates directs cell fate transitions.Nature biotechnology · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Whi3key old fashioned: a condensate cocktail for cell fate decisions.Trends in cell biology · 2026Article
- RNA helicase DDX6 governs ASC speck formation in P-bodies and the transition to stress granules via phase separation during inflammasome activation.Cell discovery · 2026Article
- SAM68 is a multifunctional post-transcriptional regulator of cardiomyocyte differentiation.Nucleic acids research · 2026Article
- tRNA synthetase activity is required for stress granule and P-body assembly.Genes & development · 2026Article
- Associations of non-HLA gene polymorphisms with celiac disease in India.Scientific reports · 2026Article
- Comprehensive Profiling of NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Lsm1-7 complex couples 3'-end protection to histone H4 acetylation to maintain mRNA homeostasis in Fusarium graminearum.Nucleic acids research · 2026Article
- Reshaping cancer cell plasticity by P-body dynamics and protein translation.Communications biology · 2026Review
- Molecular mechanisms involved inFrontiers in microbiology · 2026Review
- DDX6 undergoes phase separation to modulate metabolic plasticity and chemoresistance.Nature communications · 2025Article
- Delineating transcriptomic signatures of in vitro human skeletal muscle models in comparison to in vivo references.Stem cell reports · 2025Article
- Systematic characterization of the composition and dynamics of processing body-associated mRNAs.Nature communications · 2025Article
- Article
- Ddx61-enriched condensates refine heart regeneration programs.Nature communications · 2025Article
- Modular RNA interactions shape FXR1 condensates involved in mRNA localization and translation.Nature communications · 2025Article
- Processing bodies promote lysosomal quality control and cell survival during recovery from lysosomal damage.Research square · 2025Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 2 countries.
Bruno Di StefanoDepartment 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 02114, USA; 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.
En-Ching LuoDepartment 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.
Chuck HaggertyMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Stefan AignerDepartment 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.
Jocelyn CharltonMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Justin BrumbaughDepartment 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 02114, USA; 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.
Fei JiDepartment of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
Inés Rabano JiménezDepartment 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.
Katie J ClowersDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Aaron J HuebnerDepartment 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 02114, USA; 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.
Kendell ClementDepartment 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.
Inna LipchinaDepartment 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 02114, USA; 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.
Marit A C de KortDepartment 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 02114, USA; 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.
Anthony AnselmoDepartment of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
John PuliceDepartment 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 02114, USA; 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.
Mattia F M GerliCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
Hongcang GuDepartment 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.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Ruslan I SadreyevDepartment of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
Alexander MeissnerHarvard 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.
Gene W YeoDepartment 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 address: geneyeo@ucsd.edu.
Konrad HochedlingerDepartment 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 02114, USA; 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. Electronic address: khochedlinger@mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USUniversity of California, San Diego · USHarvard Stem Cell Institute · USMax Planck Institute for Molecular Genetics · DEBroad Institute · US
Funding
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHRISTOPHER P DUGGAN · 1994 to 2026
$31.6MRegulatory Roles and Dynamics of Nuclear long-noncoding RNAs in PluripotencyP01GM099117 · NIGMS · HARVARD UNIVERSITY · PI MEISSNER, ALEXANDER · 2011 to 2021
$21.2MRoles of sumoylation and alternative polyadenylation in cellular reprogrammingP01GM099134 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PLATH, KATHRIN · 2011 to 2021
$20.3MNew Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5MTranscription Factor Induced ReprogrammingR01HD058013 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2010 to 2019
$4.4MNICHD NIH HHS R01 HD058013NIDDK NIH HHS P30 DK040561NIGMS NIH HHS P01 GM099117NIGMS NIH HHS P01 GM099134NIGMS NIH HHS R01 GM067945
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.
Indexed as
AnimalsCell DifferentiationCell LineCell PlasticityChromatin Assembly and DisassemblyDEAD-box RNA HelicasesDNA MethylationEmbryonic Stem CellsGene Expression RegulationGene OntologyHomeostasisHumansInduced Pluripotent Stem CellsJumonji Domain-Containing Histone DemethylasesMiceMice, Inbred C57BLDDX6 protein, humanDEAD-box RNA HelicasesEDC4 protein, humanJumonji Domain-Containing Histone DemethylasesKDM4B protein, humanNanog Homeobox ProteinProteinsProto-Oncogene ProteinsRibonucleoproteinsRNA, Messengeradult progenitor cellschromatindifferentiationembryonic stem cellsexit from pluripotencynaive pluripotencyP-bodypost-transcriptional regulationprimed pluripotencyRNA helicase DDX6self-renewal
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