Polycomb repressive complex 2 component Suz12 is required for hematopoietic stem cell function and lymphopoiesis

Lee, SC; Miller, S; Hyland, C; Kauppi, M; Lebois, M; Di Rago, L; Metcalf, D; Kinkel, SA; Josefsson, EC; Blewitt, ME; Majewski, IJ; Alexander, WS

Author(s): Lee, SC; Miller, S; Hyland, C; Kauppi, M; Lebois, M; Di Rago, L; Metcalf, D; Kinkel, SA; Josefsson, EC; Blewitt, ME; Majewski, IJ; Alexander, WS;
Details: Publication Year 2015-07-09,Volume 126,Issue #2,Page 167-175
Journal Title: Blood
Publication Type: Journal Article
Abstract: Polycomb Repressive Complex 2 (PRC2) is a chromatin modifier that regulates stem cells in embryonic and adult tissues. Loss of function studies of PRC2 components has been complicated by early embryonic dependence on PRC2 activity and the partial functional redundancy of Ezh1 and Ezh2, which encode the enzymatic component of PRC2. Here, we investigated the role of PRC2 in hematopoiesis by conditional deletion of Suz12, a core component of PRC2. Complete loss of Suz12 resulted in failure of hematopoiesis, both in the embryo and the adult, with a loss of maintenance of hematopoietic stem cells (HSCs). In contrast, partial loss of PRC2 enhanced HSC self-renewal. Deletion in individual blood cell lineages revealed that, while Suz12 was required for lymphoid development, it was dispensable for the development of granulocytic, monocytic and megakaryocytic cells. Collectively, these data reveal the multi-faceted role of PRC2 in hematopoiesis, with divergent dose-dependent effects in HSC and distinct roles in maturing blood cells. Because PRC2 is a potential target for cancer therapy, the significant consequences of modest changes in PRC2 activity, as well as the cell and developmental stage-specific effects will need to be carefully considered in any therapeutic context.
Publisher: ASH
Research Division(s): Molecular Medicine; Cancer And Haematology
PubMed ID: 26036803
Publisher's Version: https://doi.org/10.1182/blood-2014-12-615898
NHMRC Grants: NHMRC/1016647, NHMRC/575500, NHMRC/1011663,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2015-06-15 09:53:27

Last Modified: 2017-07-03 09:52:55