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

被引：54

作者：

Kunimoto, Hiroyoshi ^{[1
]}

Fukuchi, Yumi ^{[1
]}

Sakurai, Masatoshi ^{[1
]}

Sadahira, Ken ^{[1
]}

Ikeda, Yasuo ^{[1
,2
]}

Okamoto, Shinichiro ^{[1
]}

Nakajima, Hideaki ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Internal Med, Div Hematol, Tokyo 1608582, Japan

[2] Waseda Univ, Fac Sci & Engn, Dept Life Sci & Med Biosci, Tokyo 1628480, Japan

来源：

SCIENTIFIC REPORTS | 2012年 / 2卷

关键词：

MUTATIONS; 5-METHYLCYTOSINE; CONVERSION; MOUSE; 5-HYDROXYMETHYLCYTOSINE; PURIFICATION; PROTEINS;

D O I：

10.1038/srep00273

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

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