Functional Comparison to Ezh2 Reveals PRC2-Independent Functions of Jarid2 in Hematopoietic Stem Cell Lineage Commitment.

Previous studies showed the Polycomb Repressive Complex 2 (PRC2) co-factor Jarid2 represses self-renewal transcriptional networks in mouse multipotent progenitor cells (MPPs). But only a fraction of de-repressed HSC-specific genes were associated with loss of H3K27me3, implying Jarid2 may have non-canonical (PRC2-indpendent) in hematopoiesis. Here we sought to delineate any PRC2-independnent functions by comparing stem and progenitor cells genetically deficient for either or (enzymatic component of PRC2). Loss of increased myeloid differentiation in transplantation assays. In contrast, loss of enhanced T-cell output. Single cell transcriptomics showed while loss of had minimal impact across progenitor populations, loss of led to accumulation of lymphoid-biased MPP4 cells and B-cell progenitors in the bone marrow. Functional assays confirmed a differentiation block at the pre-pro B-cell stage. The maturational arrest of -deficient B-cell progenitors contrasts with increased T-cell output from loss of , suggesting has non-canonical functions in hematopoiesis.