Krüppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs.
The transcription factor Klf4 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 Klf5 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.
Ema
Masatsugu
M
Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan. masaema@md.tsukuba.ac.jp
Mori
Daisuke
D
Niwa
Hitoshi
H
Hasegawa
Yoshikazu
Y
Yamanaka
Yojiro
Y
Hitoshi
Seiji
S
Mimura
Junsei
J
Kawabe
Yoh-ichi
Y
Hosoya
Tomohiro
T
Morita
Masanobu
M
Shimosato
Daisuke
D
Uchida
Kazuhiko
K
Suzuki
Norio
N
Yanagisawa
Jun
J
Sogawa
Kazuhiro
K
Rossant
Janet
J
Yamamoto
Masayuki
M
Takahashi
Satoru
S
Fujii-Kuriyama
Yoshiaki
Y
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C118391:Klf5 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; C490393:Tcl1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt