Cargando…
The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation
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 (...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406347/ https://www.ncbi.nlm.nih.gov/pubmed/32821835 http://dx.doi.org/10.1126/sciadv.abb2745 |
_version_ | 1783567400116944896 |
---|---|
author | Vizán, Pedro Gutiérrez, Arantxa Espejo, Isabel García-Montolio, Marc Lange, Martin Carretero, Ana Lafzi, Atefeh de Andrés-Aguayo, Luisa Blanco, Enrique Thambyrajah, Roshana Graf, Thomas Heyn, Holger Bigas, Anna Di Croce, Luciano |
author_facet | Vizán, Pedro Gutiérrez, Arantxa Espejo, Isabel García-Montolio, Marc Lange, Martin Carretero, Ana Lafzi, Atefeh de Andrés-Aguayo, Luisa Blanco, Enrique Thambyrajah, Roshana Graf, Thomas Heyn, Holger Bigas, Anna Di Croce, Luciano |
author_sort | Vizán, Pedro |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7406347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74063472020-08-19 The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation Vizán, Pedro Gutiérrez, Arantxa Espejo, Isabel García-Montolio, Marc Lange, Martin Carretero, Ana Lafzi, Atefeh de Andrés-Aguayo, Luisa Blanco, Enrique Thambyrajah, Roshana Graf, Thomas Heyn, Holger Bigas, Anna Di Croce, Luciano Sci Adv Research Articles 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. American Association for the Advancement of Science 2020-08-05 /pmc/articles/PMC7406347/ /pubmed/32821835 http://dx.doi.org/10.1126/sciadv.abb2745 Text en 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). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Vizán, Pedro Gutiérrez, Arantxa Espejo, Isabel García-Montolio, Marc Lange, Martin Carretero, Ana Lafzi, Atefeh de Andrés-Aguayo, Luisa Blanco, Enrique Thambyrajah, Roshana Graf, Thomas Heyn, Holger Bigas, Anna Di Croce, Luciano The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation |
title | The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation |
title_full | The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation |
title_fullStr | The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation |
title_full_unstemmed | The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation |
title_short | The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation |
title_sort | polycomb-associated factor phf19 controls hematopoietic stem cell state and differentiation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406347/ https://www.ncbi.nlm.nih.gov/pubmed/32821835 http://dx.doi.org/10.1126/sciadv.abb2745 |
work_keys_str_mv | AT vizanpedro thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT gutierrezarantxa thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT espejoisabel thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT garciamontoliomarc thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT langemartin thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT carreteroana thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT lafziatefeh thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT deandresaguayoluisa thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT blancoenrique thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT thambyrajahroshana thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT grafthomas thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT heynholger thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT bigasanna thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT dicroceluciano thepolycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT vizanpedro polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT gutierrezarantxa polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT espejoisabel polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT garciamontoliomarc polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT langemartin polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT carreteroana polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT lafziatefeh polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT deandresaguayoluisa polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT blancoenrique polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT thambyrajahroshana polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT grafthomas polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT heynholger polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT bigasanna polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation AT dicroceluciano polycombassociatedfactorphf19controlshematopoieticstemcellstateanddifferentiation |