DCAF7 regulates hematopoietic stem cell function and differentiation through polycomb repressive complex 1 (PRC1) modulation

Following transplantation, Dcaf7-deficient cells were outcompeted by wild-type cells and showed impaired self-renewal capacity. Using single-cell RNA sequencing and single-cell time-lapse microscopy, we observed that the loss of Dcaf7 accelerates the differentiation of HSCs into the myeloid lineage. At the molecular level, DCAF7 interacts with components of the E3 ligase-containing epigenetic complex polycomb repressive complex 1 (PRC1), which is involved in gene silencing, and promotes the assembly of large macromolecular PRC1 complexes.

Chromatin profiling of HSCs and progenitors revealed that the loss of DCAF7 leads to increased localization of RING1B, the core component of PRC1, at transcriptionally active genomic loci. This increased binding was observed at genes involved in myeloid differentiation and was associated with increased mRNA expression in HSCs. Together, these data reveal that DCAF7 contributes to control of HSC differentiation through the PRC1 complex.