Involvement of Ras in extraembryonic endoderm differentiation of embryonic stem cells

被引:71
作者
Yoshida-Koide, U
Matsuda, T
Saikawa, K
Nakanuma, Y
Yokota, T
Asashima, M
Koide, H
机构
[1] Kanazawa Univ, Grad Sch Med Sci, Dept Stem Cell Biol, Kanazawa, Ishikawa 9208640, Japan
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[3] Kanazawa Univ, Grad Sch Med Sci, Dept Human Pathol, Kanazawa, Ishikawa 9208640, Japan
[4] Univ Tokyo, Dept Life Sci, Tokyo 1588902, Japan
[5] Univ Tokyo, SORST JST Project, Tokyo 1588902, Japan
关键词
embryonic stem cells; Ras; differentiation; embryoid body; endoderm; Erk; Nanog;
D O I
10.1016/j.bbrc.2003.11.138
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Embryonic stem (ES) cells, derived from the inner cell mass of blastocyst can differentiate into multiple cell lineages. In this study, we examined the possible involvement of Ras in ES cell differentiation. We found that Ras was activated upon formation of embryoid bodies (EBs), an initial step in ES cell differentiation. When expressed during EB differentiation, a dominant-negative mutant of Ras suppressed induction of marker genes for extraembryonic endoderm differentiation, including GATA-4, GATA-6, alpha-fetoprotein, and hepatocyte nuclear factor 3beta, while an activated mutant promoted their induction. Expression of a Ras mutant that selectively activates the Raf/MEK/Erk pathway also enhanced induction of extraembryonic endoderm markers, and treatment with a MEK inhibitor resulted in their decreased expression. In addition, Ras stimulated downregulation of Nanog, a suppressor of endoderm differentiation in ES cells. These data suggest that Ras activation during EB differentiation plays a crucial role in initiation of extraembryonic endoderm differentiation. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:475 / 481
页数:7
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