Suchergebnisse

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. ; 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."