TET2 is essential for survival and hematopoietic stem cell homeostasis

被引：66

作者：

Shide, K. ^{[1
]}

Kameda, T. ^{[1
]}

Shimoda, H. ^{[1
]}

Yamaji, T. ^{[1
]}

Abe, H. ^{[1
]}

Kamiunten, A. ^{[1
]}

Sekine, M. ^{[1
]}

Hidaka, T. ^{[1
]}

Katayose, K. ^{[1
]}

Kubuki, Y. ^{[1
]}

Yamamoto, S. ^{[1
]}

Miike, T. ^{[1
]}

Iwakiri, H. ^{[1
]}

Hasuike, S. ^{[1
]}

Nagata, K. ^{[1
]}

Marutsuka, K. ^{[2
]}

Iwama, A. ^{[3
]}

Matsuda, T. ^{[4
]}

Kitanaka, A. ^{[1
]}

Shimoda, K. ^{[1
]}

机构：

[1] Miyazaki Univ, Fac Med, Dept Gastroenterol & Hematol, Miyazaki 8891692, Japan

[2] Miyazaki Univ, Fac Med, Dept Pathol, Miyazaki 8891692, Japan

[3] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba, Japan

[4] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Sapporo, Hokkaido, Japan

来源：

LEUKEMIA | 2012年 / 26卷 / 10期

关键词：

TET2; myeloproliferative neoplasms; tumor suppressor; animal models; hematopoietic stem cells; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; MYELOID MALIGNANCIES; GENE-EXPRESSION; MUTATION; MICE; JAK2V617F; MOUSE; 5-HYDROXYMETHYLCYTOSINE;

D O I：

10.1038/leu.2012.94

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Leukemia (2012) 26, 2216-2223; doi:10.1038/leu.2012.94

引用

页码：2216 / 2223

页数：8

共 27 条

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