Jarid2 regulates hematopoietic stem cell function by acting with polycomb repressive complex 2.

Summary, in English

Polycomb Repressive Complex 2 (PRC2) plays a key role in hematopoietic stem and progenitor cell (HSPC) function. Analyses of mouse mutants harboring deletions of core components have implicated PRC2 in fine-tuning multiple pathways that instruct HSPC behavior, yet how PRC2 is targeted to specific genomic loci within HSPCs remains unknown. Here we use shRNA-mediated knockdown to survey the function of PRC2 accessory factors that were defined in ES cells, by testing the competitive reconstitution capacity of transduced murine HSPCs. We find that similar to the phenotype observed upon depletion of core subunit Suz12, depleting Jarid2 enhances the competitive transplantation capacity of both fetal and adult mouse HSPCs. Furthermore, we demonstrate that depletion of JARID2 enhances the in vitro expansion and in vivo reconstitution capacity of human HSPCs. Gene expression profiling revealed common Suz12 and Jarid2 target genes that are enriched for the H3K27me3 mark established by PRC2. These data implicate Jarid2 as an important component of PRC2 that has a central role in coordinating HSPC function.

• Author: Sarah A Kinkel; Roman Galeev; Christoffer Flensburg; Andrew Keniry; Kelsey Breslin; Omer Gilan; Stanley Lee; Joy Liu; Kelan Chen; Linden J Gearing; Darcy L Moore; Warren S Alexander; Mark Dawson; Ian J Majewski; Alicia Oshlack; Jonas Larsson; Marnie E Blewitt
• Department/s: Division of Molecular Medicine and Gene Therapy; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publishing year: 2015
• Language: English
• Pages: 1890-1900
• Publication/Series: Blood
• Volume: 125
• Issue: 12
• Links: http://www.ncbi.nlm.nih.gov/pubmed/25645357?dopt=Abstract; http://dx.doi.org/10.1182/blood-2014-10-603969
• Document type: Journal article
• Publisher: American Society of Hematology
• Topic: Hematology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1528-0020