Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling.

Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling.
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DOI:
10.1083/jcb.200411095
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发表时间:
2005-04-25
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Sommer L
Sommer L
中科院分区:
其他
文献类型:
--
作者:
Kléber M;Lee HY;Wurdak H;Buchstaller J;Riccomagno MM;Ittner LM;Suter U;Epstein DJ;Sommer L

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典型的Wnt信号有益地促进早期神经脊干细胞(ENCSCs)的感觉神经发生(Lee,H.Y.,M.Kléber,L.Hari,V.Brault,U.Suter,M.M.Taketo,R.Kemler和L.Sommer)。2004年。科学。303:1020-1023)。然而,在正常发育过程中,Wnt信号只在eNCSC亚群中诱导感觉命运,而其他细胞保持其干细胞特征,尽管存在Wnt活性。因此,必须存在对抗Wnt信号的因子。在这里,我们显示骨形态发生蛋白信号拮抗WNT/β-连环蛋白的感觉性命运诱导活性。有趣的是,Wnt和BMP协同作用抑制分化,维持NCSC标记物的表达和多能性。与体内的神经干细胞相似,培养中的神经干细胞随着时间的推移而改变其对指导性生长因子的反应。因此,干细胞的发育受到组合生长因子活动的调控,这些活动与不断变化的细胞内在信号相互作用。
Canonical Wnt signaling instructively promotes sensory neurogenesis in early neural crest stem cells (eNCSCs) (Lee, H.Y., M. Kléber, L. Hari, V. Brault, U. Suter, M.M. Taketo, R. Kemler, and L. Sommer. 2004. Science. 303:1020–1023). However, during normal development Wnt signaling induces a sensory fate only in a subpopulation of eNCSCs while other cells maintain their stem cell features, despite the presence of Wnt activity. Hence, factors counteracting Wnt signaling must exist. Here, we show that bone morphogenic protein (BMP) signaling antagonizes the sensory fate-inducing activity of Wnt/β-catenin. Intriguingly, Wnt and BMP act synergistically to suppress differentiation and to maintain NCSC marker expression and multipotency. Similar to NCSCs in vivo, NCSCs maintained in culture alter their responsiveness to instructive growth factors with time. Thus, stem cell development is regulated by combinatorial growth factor activities that interact with changing cell-intrinsic cues.
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