Kruppel-like factor 5 Is Essential for Blastocyst Development and the Normal Self-Renewal of Mouse ESCs

被引：157

作者：

Ema, Masatsugu ^{[1
]}

Mori, Daisuke ^{[5
]}

Niwa, Hitoshi ^{[6
]}

Hasegawa, Yoshikazu ^{[1
]}

Yamanaka, Yojiro ^{[7
]}

Hitoshi, Seiji ^{[8
]}

Mimura, Junsei ^{[4
]}

Kawabe, Yoh-ichi ^{[9
]}

Hosoya, Tomohiro ^{[4
]}

Morita, Masanobu ^{[4
]}

Shimosato, Daisuke ^{[6
]}

Uchida, Kazuhiko ^{[2
,5
]}

Suzuki, Norio ^{[4
]}

Yanagisawa, Jun ^{[9
]}

Sogawa, Kazuhiro

Rossant, Janet ^{[7
,10
,11
]}

Yamamoto, Masayuki ^{[3
,4
]}

Takahashi, Satoru ^{[1
]}

Fujii-Kuriyama, Yoshiaki ^{[4
,12
]}

机构：

[1] Univ Tsukuba, Dept Anat & Embryol, Inst Basic Med Sci, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan

[2] Univ Tsukuba, Dept Mol Biol Oncol, Inst Basic Med Sci, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan

[3] Univ Tsukuba, JST ERATO Environm Response Project, Tsukuba, Ibaraki 3058575, Japan

[4] Univ Tsukuba, Tsukuba Adv Res Alliance Ctr, Tsukuba, Ibaraki 3058577, Japan

[5] Tohoku Univ, Grad Sch Life Sci, Dept Biomol Sci, Sendai, Miyagi 9808578, Japan

[6] RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Chuo Ku, Kobe, Hyogo 6500047, Japan

[7] Hosp Sick Children, Dept Mol Biol Oncol, Toronto, ON M5G 1L7, Canada

[8] Natl Inst Physiol Sci, Div Neurobiol & Bioinformat, Okazaki, Aichi 4448585, Japan

[9] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki 3058572, Japan

[10] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5G 1X8, Canada

[11] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5G 1X8, Canada

[12] Japan Sci & Technol Agcy, SORST, Kawaguchi, Saitama 3320012, Japan

来源：

CELL STEM CELL | 2008年 / 3卷 / 05期

关键词：

D O I：

10.1016/j.stem.2008.09.003

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The transcription factor KIN has demonstrated activity in the reprogramming of somatic cells to a pluripotent state, but the molecular mechanism of this process remains unknown. It is, therefore, of great interest to understand the functional role of Klf4 and related genes in ESC regulation. Here, we show that homozygous disruption of Klf5 results in the failure of ESC derivation from ICM cells and early embryonic lethality due to an implantation defect. Klf5 KO ESCs show increased expression of several differentiation marker genes and frequent, spontaneous differentiation. Conversely, overexpression of Klf5 in ESCs suppressed the expression of differentiation marker genes and maintained pluripotency in the absence of LIF. Our results also suggest that Klf6 regulates ESC proliferation by promoting phosphorylation of Akt1 via induction of Tcl1. These results, therefore, provide new insights into the functional and mechanistic role of Klf5 in regulation of pluripotency.

引用

页码：555 / 567

页数：13

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