Functional Comparison to Ezh2 Reveals PRC2-Independent Functions of Jarid2 in Hematopoietic Stem Cell Lineage Commitment
Bjeije, H.; Han, W.; Issa, N.; Krishnan, A.; Xavier Raj, I.; Arand, J.; Yang, W.; Magee, J. A.; Challen, G. A.
Show abstract
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 Jarid2 or Ezh2 (enzymatic component of PRC2). Loss of Ezh2 increased myeloid differentiation in transplantation assays. In contrast, loss of Jarid2 enhanced T-cell output. Single cell transcriptomics showed while loss of Jarid2 had minimal impact across progenitor populations, loss of Ezh2 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 Ezh2-deficient B-cell progenitors contrasts with increased T-cell output from loss of Jarid2, suggesting Jarid2 has non-canonical functions in hematopoiesis.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Lfc/Arhgef2 regulates mitotic spindle orientation in hematopoietic stem and progenitor cells and is essential for productive hematopoiesis 97%
- Gata2-regulated Gfi1b expression controls endothelial programming during endothelial-to-hematopoietic transition 96%
- Unexpected redundancy of Gpr56 and Gpr97 during hematopoietic cell development and differentiation 96%
Similar papers in this journal
- Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis 98%
- Haploinsufficiency of the essential gene RpS12 causes defects in erythropoiesis and hematopoietic stem cell maintenance 97%
- Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin-beta receptor signaling 96%
Similar papers in this journal
- Fragmentation of macrophages during isolation confounds analysis of single cell preparations from mouse hematopoietic tissues 96%
- Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction 96%
- Multipotent progenitors and hematopoietic stem cells arise independently during the endothelial to hematopoietic transition in the early mouse embryo 96%
Similar papers in this journal
- Multi-Modal Profiling of Human Fetal Liver-Derived Hematopoietic Stem Cells Reveals the Molecular Signature of Engraftment Potential 96%
- Inflammatory signals from fatty bone marrow supports the early stages of DNMT3a driven clonal hematopoiesis 96%
- Cas9-AAV6 Gene Correction of Beta-Globin in Autologous HSCs Improves Sickle Cell Disease Erythropoiesis in Mice 94%
Similar papers in this journal
- Clonal analysis of fetal hematopoietic stem/progenitor cell subsets reveals how post-transplantation capabilities are distributed 98%
- GABA produced by multiple bone marrow cell types regulates hematopoietic stem and progenitor cells 97%
- Mitochondria Regulate the Cell Fate Decisions of Megakaryocyte-Erythroid Progenitors 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.