Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells.
Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells.
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DOI：
10.1038/srep00273
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发表时间：
2012
影响因子：
4.6
通讯作者：
Nakajima, Hideaki
中科院分区：
文献类型：
--
作者：
Kunimoto, Hiroyoshi;Fukuchi, Yumi;Sakurai, Masatoshi;Sadahira, Ken;Ikeda, Yasuo;Okamoto, Shinichiro;Nakajima, Hideaki
TET 2基因体细胞突变是髓系恶性肿瘤的常见突变。最近的报道显示Tet 2的缺失导致多效造血异常，包括骨髓（BM）HSC的竞争性重建能力增加和髓样转化。然而，Tet 2缺失对胎肝（FL）HSC功能的确切影响尚未研究。在这里，我们发现Tet 2的破坏导致FL中Lin−Sca-1+c-Kit+（LSK）细胞的扩增。此外，Tet 2的缺失导致FL-HSC在体内连续移植试验中自我更新和长期再增殖能力的增强。Tet 2在FL中的破坏还导致成熟血细胞的分化改变、共同髓样祖细胞的扩增以及造血祖细胞（HPC）对体外分化刺激的抗性增加。这些结果表明，Tet 2不仅在BM中，而且在FL中在HSC和HPC的稳态中起关键作用。
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.
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DOI：
10.1634/stemcells.2008-0292
发表时间：
2009-01
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Shibata F;Goto-Koshino Y;Morikawa Y;Komori T;Ito M;Fukuchi Y;Houchins JP;Tsang M;Li DY;Kitamura T;Nakajima H
通讯作者：
Nakajima H
影响因子：
50.3
作者：
Ward PS;Patel J;Wise DR;Abdel-Wahab O;Bennett BD;Coller HA;Cross JR;Fantin VR;Hedvat CV;Perl AE;Rabinowitz JD;Carroll M;Su SM;Sharp KA;Levine RL;Thompson CB
通讯作者：
Thompson CB
内素蛋白是一种CD34样唾液素，在整个发育过程中都标志着造血干细胞。
DOI：
10.1084/jem.20051325
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
11.4
作者：
Fukuchi, Yumi;Shibata, Fumi;Nakajima, Hideaki
通讯作者：
Nakajima, Hideaki