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

Phf19, a Polycomb subunit, controls hematopoietic stem cells identity 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,...

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Detalles Bibliográficos
Autores: Vizán, Pedro|||0000-0002-6787-9940, Gutiérrez, Arantxa|||0000-0001-9033-3834, Espejo, Isabel, García-Montolio, Marc, Lange, Martin|||0000-0002-4045-3915, Carretero i Romay, Ana|||0000-0001-9377-4926, Lafzi, Atefeh|||0000-0003-4237-4847, de Andrés-Aguayo, Luisa|||0000-0001-6717-242X, Blanco, Enrique|||0000-0001-6261-7370, Thambyrajah, Roshana|||0000-0002-3941-760X, Graf, Thomas|||0000-0003-2774-4117, Heyn, Holger|||0000-0002-3276-1889, Bigas Salvans, Anna|||0000-0003-4801-6899, Di Croce, Luciano|||0000-0003-3488-6228
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:252856
Acceso en línea:https://ddd.uab.cat/record/252856
https://dx.doi.org/urn:doi:10.1126/sciadv.abb2745
Access Level:acceso abierto
Palabra clave:Taxonomy via GenBank
Nucleotide
SRA
Protein
Descripción
Sumario:Phf19, a Polycomb subunit, controls hematopoietic stem cells identity 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 (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.

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