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 (...

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Published in:Science advances 2020-08, Vol.6 (32), p.eabb2745-eabb2745
Main Authors: 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
Format: Article
Language:English
Subjects:
Epigenetics
Life Sciences
Molecular Biology
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Summary: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 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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abb2745