Signalling, cell cycle and pluripotency in embryonic stem cells

被引:577
作者
Burdon, T [1 ]
Smith, A
Savatier, P
机构
[1] Roslin Inst, Dept Gene Express & Dev, Roslin EH25 9PS, Midlothian, Scotland
[2] Univ Edinburgh, Ctr Genome Res, Edinburgh EH9 3JQ, Midlothian, Scotland
[3] Ecole Normale Super Lyon, Lab Biol Mol & Cellulaire, CNRS, UMR 5665,INRA, F-69364 Lyon 07, France
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
D O I
10.1016/S0962-8924(02)02352-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Pluripotent mouse embryonic stem (ES) cells can be expanded in large numbers in vitro owing to a process of symmetrical self-renewal. Self-renewal entails proliferation with a concomitant suppression of differentiation. Here we describe how the cytokine leukaemia inhibitory factor (LIF) sustains self-renewal through activation of the transcription factor STAT3, and how two other signals - extracellular-signal-related kinase (ERK) and phosphatidylinositol-3-OH kinase (PI3K) - can influence differentiation and propagation, respectively. We relate these observations to the unusual cell-cycle properties of ES cells and speculate on the role of the cell cycle in maintaining pluripotency.
引用
收藏
页码:432 / 438
页数:7
相关论文
共 71 条
[11]   Signaling mechanisms regulating self-renewal and differentiation of pluripotent embryonic stem cells [J].
Burdon, T ;
Chambers, I ;
Stracey, C ;
Niwa, H ;
Smith, A .
CELLS TISSUES ORGANS, 1999, 165 (3-4) :131-143
[12]   Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6 [J].
Chen, PL ;
Riley, DJ ;
ChenKiang, S ;
Lee, WH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) :465-469
[13]   Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs [J].
Chen, PL ;
Riley, DJ ;
Chen, YM ;
Lee, WH .
GENES & DEVELOPMENT, 1996, 10 (21) :2794-2804
[14]   Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation [J].
Cheng, AM ;
Saxton, TM ;
Sakai, R ;
Kulkarni, S ;
Mbamalu, G ;
Vogel, W ;
Tortorice, CG ;
Cardiff, RD ;
Cross, JC ;
Muller, WJ ;
Pawson, T .
CELL, 1998, 95 (06) :793-803
[15]   Ablation of the Retinoblastoma gene family deregulates G1 control causing immortalization and increased cell turnover under growth-restricting conditions [J].
Dannenberg, JH ;
van Rossum, A ;
Schuijff, L ;
Riele, HT .
GENES & DEVELOPMENT, 2000, 14 (23) :3051-3064
[16]   LIFR-BETA AND GP-130 AS HETERODIMERIZING SIGNAL TRANSDUCERS OF THE TRIPARTITE CNTF RECEPTOR [J].
DAVIS, S ;
ALDRICH, TH ;
STAHL, N ;
PAN, L ;
TAGA, T ;
KISHIMOTO, T ;
IP, NY ;
YANCOPOULOS, GD .
SCIENCE, 1993, 260 (5115) :1805-1808
[17]   Glycogen synthase kinase 3β regulates cyclin D1 proteolysis and subcellular localization [J].
Diehl, JA ;
Cheng, MG ;
Roussel, MF ;
Sherr, CJ .
GENES & DEVELOPMENT, 1998, 12 (22) :3499-3511
[18]  
DOETSCHMAN TC, 1985, J EMBRYOL EXP MORPH, V87, P27
[19]   Cyclin E in human cancers [J].
Donnellan, R ;
Chetty, R .
FASEB JOURNAL, 1999, 13 (08) :773-780
[20]   The carboxyl-terminal domains of gp130-related cytokine receptors are necessary for suppressing embryonic stem cell differentiation - Involvement of STAT3 [J].
Ernst, M ;
Novak, U ;
Nicholson, SE ;
Layton, JE ;
Dunn, AR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (14) :9729-9737