The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Vizán, Pedro
  • dc.contributor.author Gutiérrez, Arantxa
  • dc.contributor.author Espejo, Isabel
  • dc.contributor.author García Montolío, Marc, 1991-
  • dc.contributor.author Lange, Martin
  • dc.contributor.author Carretero, Ana
  • dc.contributor.author Lafzi, Atefeh
  • dc.contributor.author Andrés Aguayo, Luisa de
  • dc.contributor.author Blanco, Enrique
  • dc.contributor.author Thambyrajah, Roshana
  • dc.contributor.author Graf, T. (Thomas)
  • dc.contributor.author Heyn, Holger
  • dc.contributor.author Bigas Salvans, Anna
  • dc.contributor.author Di Croce, Luciano
  • dc.date.accessioned 2020-11-02T06:52:42Z
  • dc.date.available 2020-11-02T06:52:42Z
  • dc.date.issued 2020
  • dc.description.abstract Adult hematopoietic stem cells (HSCs) are rare multipotent cells in bone marrow that are responsible for generating all blood cell types. HSCs are a heterogeneous group of cells with high plasticity, in part, conferred by epigenetic mechanisms. PHF19, a subunit of the Polycomb repressive complex 2 (PRC2), is preferentially expressed in mouse hematopoietic precursors. Here, we now show that, in stark contrast to results published for other PRC2 subunits, genetic depletion of Phf19 increases HSC identity and quiescence. While proliferation of HSCs is normally triggered by forced mobilization, defects in differentiation impede long-term correct blood production, eventually leading to aberrant hematopoiesis. At molecular level, PHF19 deletion triggers a redistribution of the histone repressive mark H3K27me3, which notably accumulates at blood lineage-specific genes. Our results provide novel insights into how epigenetic mechanisms determine HSC identity, control differentiation, and are key for proper hematopoiesis.
  • dc.description.sponsorship The work in the Di Croce laboratory is supported by grants from the Spanish of Economy, Industry, and Competitiveness (MEIC) (BFU2016-75008-P), “Fundación Vencer El Cancer” (VEC), the European Regional Development Fund (FEDER), Fundació “La Marató de TV3,” and from AGAUR. The laboratory of A.B. is supported by SAF2016-75613-R from the Ministerio de Ciencia, Innovación y Universidades. H.H. is a Miguel Servet (CP14/00229) researcher funded by the Spanish Institute of Health Carlos III (ISCIII) and received funding from the European Union’s Horizon 2020 research and innovation programme (MSCA-ITN-2015-675752) and the Ministerio de Ciencia, Innovación y Universidades (SAF2017-89109-P; AEI/FEDER, UE). P.V. was supported by “Fundación Científica de la Asociación Española Contra el Cáncer.”
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Vizán P, Gutiérrez A, Espejo I, García-Montolio M, Lange M, Carretero A, Lafzi A, de Andrés-Aguayo L, Blanco E, Thambyrajah R, Graf T, Heyn H, Bigas A, Di Croce L. The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation. Sci Adv. 2020; 6(32):eabb2745. DOI: 10.1126/sciadv.abb2745
  • dc.identifier.doi http://dx.doi.org/10.1126/sciadv.abb2745
  • dc.identifier.issn 2375-2548
  • dc.identifier.uri http://hdl.handle.net/10230/45628
  • dc.language.iso eng
  • dc.publisher American Association for the Advancement of Science (AAAS)
  • dc.relation.ispartof Sci Adv. 2020; 6(32):eabb2745
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/675752
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-75008-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75613-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-89109-P
  • dc.rights Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
  • dc.title The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Departament de Medicina i Ciències de la Vida)
Articles (Center for Genomic Regulation (CRG))
Articles (Hospital del Mar Research Institute)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)