モチヅキ　マキコ   望月　牧子    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Dependency on the polycomb gene Ezh2 distinguishes fetal from adult hematopoietic stem cells.
掲載誌名	正式名：Blood 略　 称：Blood ISSNコード：15280020/00064971
掲載区分	国外
巻・号・頁	118(25),pp.6553-61
著者・共著者	Mochizuki-Kashio Makiko, Mishima Yuta, Miyagi Satoru, Negishi Masamitsu, Saraya Atsunori, Konuma Takaaki, Shinga Jun, Koseki Haruhiko, Iwama Atsushi
発行年月	2011/12
概要	Polycomb-group (PcG) proteins are essential regulators of hematopoietic stem cells (HSCs). In contrast to Bmi1, a component of Polycomb repressive complex 1 (PRC1), the role of PRC2 and its components in hematopoiesis remains elusive. Here we show that Ezh2, a core component of PRC2, is essential for fetal, but not adult, HSCs. Ezh2-deficient embryos died of anemia because of insufficient expansion of HSCs/progenitor cells and defective erythropoiesis in fetal liver. Deletion of Ezh2 in adult BM, however, did not significantly compromise hematopoiesis, except for lymphopoiesis. Of note, Ezh2-deficient fetal liver cells showed a drastic reduction in trimethylation of histone H3 at lysine 27 (H3K27me3) accompanied by derepression of a large cohort of genes, whereas on homing to BM, they acquired a high level of H3K27me3 and long-term repopulating capacity. Quantitative RT-PCR revealed that Ezh1, the gene encoding a backup enzyme, is highly expressed in HSCs/progenitor cells in BM compared with those in fetal liver, whereas Ezh2 is ubiquitously expressed. These findings suggest that Ezh1 complements Ezh2 in the BM, but not in the fetal liver, and reveal that the reinforcement of PcG-mediated gene silencing occurs during the transition from proliferative fetal HSCs to quiescent adult HSCs.
DOI	10.1182/blood-2011-03-340554
PMID	22042701