Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells

Hiroyoshi Kunimoto, Yumi Fukuchi, Masatoshi Sakurai, Ken Sadahira, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Somatic mutation of ten-eleven translocation 2 (TET2) gene is frequently found in human myeloid malignancies. Recent reports showed that loss of Tet2 led to pleiotropic hematopoietic abnormalities including increased competitive repopulating capacity of bone marrow (BM) HSCs and myeloid transformation. However, precise impact of Tet2 loss on the function of fetal liver (FL) HSCs has not been examined. Here we show that disruption of Tet2 results in the expansion of Lin -Sca-1 + c-Kit +(LSK) cells in FL. Furthermore, Tet2 loss led to enhanced self-renewal and long-term repopulating capacity of FL-HSCs in in vivo serial transplantation assay. Disruption of Tet2 in FL also led to altered differentiation of mature blood cells, expansion of common myeloid progenitors and increased resistance for hematopoietic progenitor cells (HPCs) to differentiation stimuli in vitro. These results demonstrate that Tet2 plays a critical role in homeostasis of HSCs and HPCs not only in the BM, but also in FL.

Original languageEnglish
Article number273
JournalScientific Reports
Volume2
DOIs
Publication statusPublished - 2012

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Hematopoietic Stem Cells
Liver
Bone Marrow
Myeloid Progenitor Cells
Cell Differentiation
Blood Cells
Homeostasis
Transplantation
Mutation
Genes
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells. / Kunimoto, Hiroyoshi; Fukuchi, Yumi; Sakurai, Masatoshi; Sadahira, Ken; Ikeda, Yasuo; Okamoto, Shinichiro; Nakajima, Hideaki.

In: Scientific Reports, Vol. 2, 273, 2012.

Research output: Contribution to journalArticle

Kunimoto, Hiroyoshi ; Fukuchi, Yumi ; Sakurai, Masatoshi ; Sadahira, Ken ; Ikeda, Yasuo ; Okamoto, Shinichiro ; Nakajima, Hideaki. / Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells. In: Scientific Reports. 2012 ; Vol. 2.
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AU - Ikeda, Yasuo

AU - Okamoto, Shinichiro

AU - Nakajima, Hideaki

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