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

Pedro Vizán, Arantxa Gutiérrez, Isabel Espejo, Marc García-Montolio, Martin Lange, Ana Carretero, Atefeh Lafzi, Luisa de Andrés-Aguayo, Enrique Blanco, Roshana Thambyrajah, Thomas Graf, Holger Heyn, Anna Bigas, Luciano Di Croce

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageAmerican English
Pages (from-to)eabb2745
JournalScience advances
Volume6
Issue number32
DOIs
Publication statusPublished - 1 Aug 2020

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