title: TET2 is essential for survival and hematopoietic stem cell homeostasis.
abstract: Ten-Eleven-Translocation 2 (TET2) is an enzyme that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5-hmC) and thereby alters the epigenetic state of DNA; somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies. To study the function of TET2 in vivo, we analyzed Ayu17-449 (TET2(trap)) mice, in which a gene trap insertion in intron 2 of TET2 reduces TET2 mRNA levels to about 20% of that found in wild-type (WT) mice. TET2(trap/trap) mice were born at Mendelian frequency but died at a high rate by postnatal day 3, indicating the essential role of TET2 for survival. Loss of TET2 results in an increase in the number of hematopoietic stem cells (HSCs)/progenitors in the fetal liver, and TET2(trap/trap) HSCs exhibit an increased self-renewal ability in vivo. In competitive transplantation assays, TET2(trap/trap) HSCs possess a competitive growth advantage over WT HSCs. These data indicate that TET2 has a critical role in survival and HSC homeostasis.
authors.affiliation: Department of Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, Kiyotake, Miyazaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shide
authors.forename: T
authors.initials: T
authors.lastname: Kameda
authors.forename: H
authors.initials: H
authors.lastname: Shimoda
authors.forename: T
authors.initials: T
authors.lastname: Yamaji
authors.forename: H
authors.initials: H
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Kamiunten
authors.forename: M
authors.initials: M
authors.lastname: Sekine
authors.forename: T
authors.initials: T
authors.lastname: Hidaka
authors.forename: K
authors.initials: K
authors.lastname: Katayose
authors.forename: Y
authors.initials: Y
authors.lastname: Kubuki
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Miike
authors.forename: H
authors.initials: H
authors.lastname: Iwakiri
authors.forename: S
authors.initials: S
authors.lastname: Hasuike
authors.forename: K
authors.initials: K
authors.lastname: Nagata
authors.forename: K
authors.initials: K
authors.lastname: Marutsuka
authors.forename: A
authors.initials: A
authors.lastname: Iwama
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: A
authors.initials: A
authors.lastname: Kitanaka
authors.forename: K
authors.initials: K
authors.lastname: Shimoda
mesh_terms: D000818:Animals; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000502:physiology*; D049308:Dioxygenases; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006706:Homeostasis; D053614:Janus Kinase 2 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D049308:Dioxygenases; C551914:Tet2 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2