title: Jarid2 regulates hematopoietic stem cell function by acting with polycomb repressive complex 2.
abstract: 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 short hairpin RNA-mediated knockdown to survey the function of PRC2 accessory factors that were defined in embryonic stem cells (ESCs) 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.
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Sarah A
authors: SA
authors: Kinkel
authors: Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden;
authors: Roman
authors: R
authors: Galeev
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia; Bioinformatics, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; and.
authors: Christoffer
authors: C
authors: Flensburg
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Andrew
authors: A
authors: Keniry
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia;
authors: Kelsey
authors: K
authors: Breslin
authors: Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
authors: Omer
authors: O
authors: Gilan
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Stanley
authors: S
authors: Lee
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia;
authors: Joy
authors: J
authors: Liu
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Kelan
authors: K
authors: Chen
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Linden J
authors: LJ
authors: Gearing
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Darcy L
authors: DL
authors: Moore
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Warren S
authors: WS
authors: Alexander
authors: Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
authors: Mark
authors: M
authors: Dawson
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Ian J
authors: IJ
authors: Majewski
authors: Bioinformatics, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; and.
authors: Alicia
authors: A
authors: Oshlack
authors: Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden;
authors: Jonas
authors: J
authors: Larsson
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;
authors: Marnie E
authors: ME
authors: Blewitt
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D019070:Cell Lineage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010641:Phenotype; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
chemical_list: D018952:Antigens, CD34; C547777:JARID2 protein, human; C093650:Jarid2 protein, mouse; D034741:RNA, Small Interfering; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2
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