セラ　ヤスユキ   Sera Yasuyuki   世良　康如    所属   研究施設 研究施設    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	UTX maintains the functional integrity of the murine hematopoietic system by globally regulating aging-associated genes.
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	137(7),pp.908-922
著者・共著者	Sera Yasuyuki†, Nakata yuichiro, Ueda Takeshi, Yamasaki norimasa, Koide shuhei, Kobayashi hiroshi, Ikeda kenichiro, Kobatake Kohei, Iwasaki Masayuki, Oda Hideaki, Wolff Linda, Kanai Akinori, Nagamachi Akiko, Inaba Toshiya, Sotomaru Yusuke, Ichinohe Tatsuo, Koizumi Miho, Miyakawa Yoshihiko, Honda Zenichiro, Iwama Atsushi, Suda Toshio, Takubo Keiyo, Honda Hiroaki
担当区分	筆頭著者
発行年月	2021/02
概要	Epigenetic regulation is essential for the maintenance of the hematopoietic system, and its deregulation is implicated in hematopoietic disorders. In this study, UTX, a demethylase for lysine 27 on histone H3 (H3K27) and a component of COMPASS-like and SWI/SNF complexes, played an essential role in the hematopoietic system by globally regulating aging-associated genes. Utx-deficient (UtxΔ/Δ) mice exhibited myeloid skewing with dysplasia, extramedullary hematopoiesis, impaired hematopoietic reconstituting ability, and increased susceptibility to leukemia, which are the hallmarks of hematopoietic aging. RNA-sequencing (RNA-seq) analysis revealed that Utx deficiency converted the gene expression profiles of young hematopoietic stem-progenitor cells (HSPCs) to those of aged HSPCs. Utx expression in hematopoietic stem cells declined with age, and UtxΔ/Δ HSPCs exhibited increased expression of an aging-associated marker, accumulation of reactive oxygen species, and impaired repair of DNA double-strand breaks. Pathway and chromatin immunoprecipitation analyses coupled with RNA-seq data indicated that UTX contributed to hematopoietic homeostasis mainly by maintaining the expression of genes downregulated with aging via demethylase-dependent and -independent epigenetic programming. Of note, comparison of pathway changes in UtxΔ/Δ HSPCs, aged muscle stem cells, aged fibroblasts, and aged induced neurons showed substantial overlap, strongly suggesting common aging mechanisms among different tissue stem cells.
DOI	10.1182/blood.2019001044
PMID	33174606