The Polycomb-Associated Factor Phf19 Controls Hematopoietic Stem Cell Status 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 show that genetic deletion of Phf19 increases HSC specific status. 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 the molecular level, PHF19 controls deposition of the histone repressive mark H3K27me3, which accumulates in blood lineage-specific genes. Our results identify PHF19 as having a key role in regulating the epigenetic landscape of HSCs, thus permitting proper blood production. Overall design: ChIP-seq for H3K27me3 (4 samples), RNA-seq (4 samples), MARS-Seq (4 samples) and ATAC-seq (2 samples) of HSCs. FF means Floxed-condition (Control) and KO means PHF19 KO mice.