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
[31]   Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2 [J].
Kobayashi, T ;
Cohen, P .
BIOCHEMICAL JOURNAL, 1999, 339 :319-328
[32]   Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions [J].
Kolch, W .
BIOCHEMICAL JOURNAL, 2000, 351 :289-305
[33]   Cyclin D1 expression is regulated positively by the p42/p44(MAPK) and negatively by the p38/HOG(MAPK) pathway [J].
Lavoie, JN ;
LAllemain, G ;
Brunet, A ;
Muller, R ;
Pouyssegur, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (34) :20608-20616
[34]  
LeCouter JE, 1996, ONCOGENE, V12, P1433
[35]   RETINOBLASTOMA-PROTEIN-DEPENDENT CELL-CYCLE INHIBITION BY THE TUMOR-SUPPRESSOR P16 [J].
LUKAS, J ;
PARRY, D ;
AAGAARD, L ;
MANN, DJ ;
BARTKOVA, J ;
STRAUSS, M ;
PETERS, G ;
BARTEK, J .
NATURE, 1995, 375 (6531) :503-506
[36]   STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells [J].
Matsuda, T ;
Nakamura, T ;
Nakao, K ;
Arai, T ;
Katsuki, M ;
Heike, T ;
Yokota, T .
EMBO JOURNAL, 1999, 18 (15) :4261-4269
[37]   GROWTH SUPPRESSION BY P16(INK4) REQUIRES FUNCTIONAL RETINOBLASTOMA PROTEIN [J].
MEDEMA, RH ;
HERRERA, RE ;
LAM, F ;
WEINBERG, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (14) :6289-6293
[38]   Introducing embryonic stem cells [J].
Nichols, J .
CURRENT BIOLOGY, 2001, 11 (13) :R503-R505
[39]   Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3 [J].
Niwa, H ;
Burdon, T ;
Chambers, I ;
Smith, A .
GENES & DEVELOPMENT, 1998, 12 (13) :2048-2060
[40]   pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation [J].
Novitch, BG ;
Spicer, DB ;
Kim, PS ;
Cheung, WL ;
Lassar, AB .
CURRENT BIOLOGY, 1999, 9 (09) :449-459