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

Masatsugu Ema, Daisuke Mori, Hitoshi Niwa, Yoshikazu Hasegawa, Yojiro Yamanaka, Seiji Hitoshi, Junsei Mimura, Yoh ichi Kawabe, Tomohiro Hosoya, Masanobu Morita, Daisuke Shimosato, Kazuhiko Uchida, Norio Suzuki, Jun Yanagisawa, Kazuhiro Sogawa, Janet Rossant, Masayuki Yamamoto, Satoru Takahashi, Yoshiaki Fujii-Kuriyama

Research output: Contribution to journalArticlepeer-review

150 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)555-567
Number of pages13
JournalCell Stem Cell
Volume3
Issue number5
DOIs
Publication statusPublished - 2008 Nov 6

Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Krüppel-like factor 5 Is Essential for Blastocyst Development and the Normal Self-Renewal of Mouse ESCs'. Together they form a unique fingerprint.

Cite this