biostudies-literatureUnknownBjeije HNIDDK NIH HHSNHLBI NIH HHSNCI NIH HHSPrevious 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 <i>Jarid2</i> or <i>Ezh2</i> (enzymatic component of PRC2). Loss of <i>Ezh2</i> increased myeloid differentiation in transplantation assays. In contrast, loss of <i>Jarid2</i> enhanced T-cell output. Single cell transcriptomics showed while loss of <i>Jarid2</i> had minimal impact across progenitor populations, loss of <ibioRxiv : the preprint server for biology2025.07.18.665536https://www.ebi.ac.uk/biostudies/studies/S-EPMC12338735biostudies-literatureFunctional Comparison to Ezh2 Reveals PRC2-Independent Functions of Jarid2 in Hematopoietic Stem Cell Lineage Commitment.PMC12338735R01 HL147978P30 CA091842R01 CA236819R01 DK124883R01 HL152180Raj IXChallen GAYang WLi YMagee JAArand JHan WIssa NBjeije HKrishnan AfalseFunctional 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 <i>Jarid2</i> or <i>Ezh2</i> (enzymatic component of PRC2). Loss of <i>Ezh2</i> increased myeloid differentiation in transplantation assays. In contrast, loss of <i>Jarid2</i> enhanced T-cell output. Single cell transcriptomics showed while loss of <i>Jarid2</i> had minimal impact across progenitor populations, loss of <i2025-01-01T00:00:00Z2025 Jul2026-04-08T03:50:12.774Z2026-04-07T21:41:37.966ZS-EPMC123387354079153510.1101/2025.07.18.665536