Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development.
Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development.
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DOI：
10.1016/j.stem.2011.07.010
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发表时间：
2011-08-05
期刊：
影响因子：
23.9
通讯作者：
Jaenisch, Rudolf
中科院分区：
文献类型：
--
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
酶的泰特家族（Tet 1/2/3）将5-甲基胞嘧啶（5 mC）转化为5-羟甲基胞嘧啶（5 hmC）。小鼠胚胎干细胞（mESC）高度表达Tet 1，并具有升高的5 hmC水平。Tet 1与体外ESC维持和谱系特化有关，但其在发育中的确切功能尚未明确。为了确定Tet 1在多能性和发育中的作用，我们已经产生了Tet 1突变体mESC和小鼠。Tet 1 −/− ESCs具有降低的5 hmC水平，全局基因表达的细微变化，是多能的，并在四倍体互补试验中支持活产小鼠的发育，但在体外显示出向滋养外胚层的偏斜分化。Tet 1突变小鼠是可行的，可生育的和大体上正常的，尽管一些突变小鼠在出生时体型略小。我们的数据表明，Tet 1的损失导致5 hmC水平的部分减少，不影响胚胎干细胞的多能性，是与胚胎和出生后的发展。
The Tet family of enzymes (Tet1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Mouse embryonic stem cells (mESCs) highly express Tet1 and have an elevated level of 5hmC. Tet1 has been implicated in ESC maintenance and lineage specification in vitro but its precise function in development is not well defined. To establish the role of Tet1 in pluripotency and development we have generated Tet1 mutant mESCs and mice. Tet1−/− ESCs have reduced levels of 5hmC, subtle changes in global gene expression, are pluripotent and support development of live-born mice in tetraploid complementation assay but display skewed differentiation towards trophectoderm in vitro. Tet1 mutant mice are viable, fertile and grossly normal though some mutant mice have a slightly smaller body size at birth. Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development.
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影响因子：
4.8
作者：
Dawlaty, Meelad M.;van Deursen, Jan M.
通讯作者：
van Deursen, Jan M.
影响因子：
11.2
作者：
Valinluck, Victoria;Sowers, Lawrence C.
通讯作者：
Sowers, Lawrence C.
DOI：
10.1126/science.1170116
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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Rao A
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64.5
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影响因子：
64.8
作者：
Wu, Hao;D'Alessio, Ana C.;Ito, Shinsuke;Xia, Kai;Wang, Zhibin;Cui, Kairong;Zhao, Keji;Sun, Yi Eve;Zhang, Yi
通讯作者：
Zhang, Yi