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

Kinkel, Sarah A; Galeev, Roman LU ; Flensburg, Christoffer; Keniry, Andrew; Breslin, Kelsey; Gilan, Omer; Lee, Stanley; Liu, Joy; Chen, Kelan and Gearing, Linden J, et al. (2015) In Blood 125(12). p.1890-1900
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 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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
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Blood
volume
125
issue
12
pages
1890 - 1900
publisher
American Society of Hematology
external identifiers
  • pmid:25645357
  • wos:000354623700012
  • scopus:84925356017
ISSN
1528-0020
DOI
10.1182/blood-2014-10-603969
language
English
LU publication?
yes
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d339b6aa-6705-4807-a305-2b5bbbd50aac (old id 5145623)
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http://www.ncbi.nlm.nih.gov/pubmed/25645357?dopt=Abstract
date added to LUP
2015-03-03 16:46:58
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2017-08-06 03:02:31
@article{d339b6aa-6705-4807-a305-2b5bbbd50aac,
  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 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       = {Kinkel, Sarah A and Galeev, Roman and Flensburg, Christoffer and Keniry, Andrew and Breslin, Kelsey and Gilan, Omer and Lee, Stanley and Liu, Joy and Chen, Kelan and Gearing, Linden J and Moore, Darcy L and Alexander, Warren S and Dawson, Mark and Majewski, Ian J and Oshlack, Alicia and Larsson, Jonas and Blewitt, Marnie E},
  issn         = {1528-0020},
  language     = {eng},
  number       = {12},
  pages        = {1890--1900},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Jarid2 regulates hematopoietic stem cell function by acting with polycomb repressive complex 2.},
  url          = {http://dx.doi.org/10.1182/blood-2014-10-603969},
  volume       = {125},
  year         = {2015},
}