@article{10902/37549,
year = {2020},
url = {https://hdl.handle.net/10902/37549},
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.},
organization = {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.” I.E. was supported by La Caixa INPhINIT program. M.G.-M. was
supported by the FPI Program, and R.T. was supported by Generalitat de Catalunya (Beatriu de
Pinós program; 2016 BP 00021). We acknowledge support from the Spanish MEIC through the
Instituto de Salud Carlos III and the EMBL partnership, Centro de Excelencia Severo Ochoa,
CERCA Programme/Generalitat de Catalunya, the Generalitat de Catalunya through
Departament de Salut and Departament d’Empresa i Coneixement, and the Co-financing by the
Spanish Ministry of Economy, Industry and Competitiveness (MEIC) with funds from the
European Regional Development Fund (ERDF) corresponding to the 2014-2020 Smart Growth
Operating Program.},
publisher = {American Association for the Advancement of Science},
publisher = {Science Advances, 2020, 6(32), eabb2745},
title = {The Polycomb-associated factor PHF19 controls hematopoietic stem cell state and differentiation},
author = {Vizán, Pedro and Gutiérrez, Arantxa and Espejo, Isabel and García Montolio, Marc and Lange, Martin and Carretero, Ana and Lafzi, Atefeh and De Andrés Aguayo, Luisa and Blanco, Enrique and Thambyrajah, Roshana and Graf, Thomas and Heyn, Holger and Bigas, Anna and Di Croce, Luciano},
}