Open AccessActivation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells
Author(s) -
Satoshi Watanabe,
Hiroki Umehara,
Kazushige Murayama,
Masaru Okabe,
Tohru Kimura,
Toru Nakano
Publication year - 2006
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/sj.onc.1209307
Subject(s) - biology , protein kinase b , pi3k/akt/mtor pathway , embryonic stem cell , stem cell , microbiology and biotechnology , leukemia inhibitory factor , induced pluripotent stem cell , proto oncogene proteins c akt , homeobox protein nanog , signal transduction , genetics , gene
Embryonic stem (ES) cells can self-renew indefinitely without losing their differentiation ability to any cell types. Phosphoinositide-3 kinase (PI3K)/Akt signaling plays a pivotal role in various stem cell systems, including the formation of embryonic germ (EG) cells from primordial germ cells and self-renewal of neural stem cells. Here, we show that myristoylated, active form of Akt (myr-Akt) maintained the undifferentiated phenotypes in mouse ES cells without the addition of leukemia inhibitory factor (LIF). The effects of myr-Akt were reversible, because LIF dependence and pluripotent differentiation activity were restored by the deletion of myr-Akt. In addition, myr-Akt-Mer fusion protein, whose enzymatic activity is controlled by 4-hydroxy-tamoxifen, also maintained the pluripotency of not only mouse but also cynomolgus monkey ES cells. These results clearly demonstrate that Akt signaling sufficiently maintains pluripotency in mouse and primate ES cells, and support the notion that PI3K/Akt signaling axis regulates 'stemness' in a broad spectrum of stem cell systems.