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Acute Leukemias

TET2 is essential for survival and hematopoietic stem cell homeostasis

Leukemia volume 26, pages 2216–2223 (2012)Cite this article

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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 (TET2trap) 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. TET2trap/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 TET2trap/trap HSCs exhibit an increased self-renewal ability in vivo. In competitive transplantation assays, TET2trap/trap HSCs possess a competitive growth advantage over WT HSCs. These data indicate that TET2 has a critical role in survival and HSC homeostasis.

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Acknowledgements

We thank M Matsushita, T Shinmori, E Torii for their technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research (numbers 20591137, 2110490, 20890176, 23591397) from the Ministry of Education, Science, Sports, and Culture in Japan, and a Grant-in-Aid from the Tokyo Biochemical Research Foundation, Tokyo, Japan.

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Authors and Affiliations

  1. Department of Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, Kiyotake, Miyazaki, Japan

    K Shide, T Kameda, H Shimoda, T Yamaji, H Abe, A Kamiunten, M Sekine, T Hidaka, K Katayose, Y Kubuki, S Yamamoto, T Miike, H Iwakiri, S Hasuike, K Nagata, A Kitanaka & K Shimoda

  2. Department of Pathology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan

    K Marutsuka

  3. Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

    A Iwama

  4. Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    T Matsuda

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  1. K Shide
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Correspondence to K Shimoda.

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Shide, K., Kameda, T., Shimoda, H. et al. TET2 is essential for survival and hematopoietic stem cell homeostasis. Leukemia 26, 2216–2223 (2012). https://doi.org/10.1038/leu.2012.94

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