Spatial organization of embryonic stem cell responsiveness to autocrine gp130 ligands reveals an autoregulatory stem cell niche

被引:46
作者
Davey, Ryan E.
Zandstra, Peter W.
机构
[1] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3C9, Canada
[2] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3C9, Canada
关键词
autocrine signaling; embryonic stem cell; niche; self-renewal; stem cell biology;
D O I
10.1634/stemcells.2006-0216
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Highly ordered aggregates of cells, or niches, regulate stem cell fate. Specific tissue location need not be an obligatory requirement for a stem cell niche, particularly during embryogenesis, where cells exist in a dynamic environment. We investigated autoregulatory fixed-location-independent processes controlling cell fate by analyzing the spatial organization of embryonic stem cells (ESCs) using quantitative single-cell immunocytochemistry and a computational approach involving Delaunay triangulation. ESC colonies demonstrated radial organization of phosphorylated signal transducer and activator of transcription 3, Nanog, and Oct4 ( among others) in the presence and absence of exogenous leukemia inhibitory factor (LIF). Endogenous self-renewal signaling resulted from autocrine non-LIF gp130 ligands, which buffered cells against differentiation upon exogenous LIF deprivation. Together with a radial organization of differential responsiveness to gp130 ligands within colonies, autocrine signaling produced a radial organization of self-renewal, generating a fixed-location-independent autoregulatory niche. These findings reveal fundamental properties of niches and elucidate mechanisms colonies of cells use to transition between fates during morphogenesis.
引用
收藏
页码:2538 / 2548
页数:11
相关论文
共 58 条
[1]   Stem cells of the skin epithelium [J].
Alonso, L ;
Fuchs, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 :11830-11835
[2]   Autoregulation of pituitary corticotroph SOCS-3 expression: Characterization of the murine SOCS-3 promoter [J].
Auernhammer, CJ ;
Bousquet, C ;
Melmed, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :6964-6969
[3]   Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells [J].
Burdon, T ;
Stracey, C ;
Chambers, I ;
Nichols, J ;
Smith, A .
DEVELOPMENTAL BIOLOGY, 1999, 210 (01) :30-43
[4]   Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells [J].
Chambers, I ;
Colby, D ;
Robertson, M ;
Nichols, J ;
Lee, S ;
Tweedie, S ;
Smith, A .
CELL, 2003, 113 (05) :643-655
[5]   Quantitative screening of embryonic stem cell differentiation: Endoderm formation as a model [J].
Chang, KH ;
Zandstra, PW .
BIOTECHNOLOGY AND BIOENGINEERING, 2004, 88 (03) :287-298
[6]  
CONOVER JC, 1993, DEVELOPMENT, V119, P559
[7]   SIGNALS FOR DEATH AND SURVIVAL - A 2-STEP MECHANISM FOR CAVITATION IN THE VERTEBRATE EMBRYO [J].
COUCOUVANIS, E ;
MARTIN, GR .
CELL, 1995, 83 (02) :279-287
[8]   Paracrine induction of stem cell renewal by LIF-deficient cells: A new ES cell regulatory pathway [J].
Dani, C ;
Chambers, I ;
Johnstone, S ;
Robertson, M ;
Ebrahimi, B ;
Saito, M ;
Taga, T ;
Li, M ;
Burdon, T ;
Nichols, J ;
Smith, A .
DEVELOPMENTAL BIOLOGY, 1998, 203 (01) :149-162
[9]   Signal processing underlying extrinsic control of stem cell fate [J].
Davey, RE ;
Zandstra, PW .
CURRENT OPINION IN HEMATOLOGY, 2004, 11 (02) :95-101
[10]   ESTABLISHMENT IN CULTURE OF PLURIPOTENTIAL CELLS FROM MOUSE EMBRYOS [J].
EVANS, MJ ;
KAUFMAN, MH .
NATURE, 1981, 292 (5819) :154-156