IWASAKI Masayuki    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	UTX maintains the functional integrity of the murine hematopoietic system by globally regulating aging-associated genes.
Journal	Formal name：Blood Abbreviation：Blood ISSN code：15280020/00064971
Domestic / Foregin	Foregin
Volume, Issue, Page	137(7),pp.908-922
Author and coauthor	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
Publication date	2021/02
Summary	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