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Notch蛋白促使神经系统干细胞的分化
http://www.100md.com 2006年4月26日 丁香园
     爱丁堡大学的研究人员最近的研究发现,80年前首先在果蝇中发现Notch蛋白可以调控未分化的胚胎干细胞向神经系统的分化。

    胚胎干细胞可以分化成为机体中的200种细胞,科学家一直希望通过研究揭示维持胚胎干细胞多样性的方法及找出诱导其分化的信号分子,而最近的研究结果表明,Notch蛋白可以诱导其向神经细胞的定向分化。

    研究显示,Notch蛋白如果被表达,则90%的胚胎干细胞将定向分化为神经细胞,而在同等条件下的对照组中,大部分将不会定向的分化,而是随机的分化为其他种类的细胞或维持未分化状态。

    这种Notch蛋白在人和鼠的胚胎干细胞中都得到验证。

    Notch Promotes Neural Lineage Entry by Pluripotent Embryonic Stem Cells

    Sally Lowell1*, Alexandra Benchoua1,2, Barry Heavey1, Austin G. Smith1,3*

    1 Centre Development in Stem Cell Biology, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom, 2 INSERM U 421/I-STEM, Faculté de Médecine, Evry-Cedex, France, 3 Institute for Stem Cell Biology, University of Cambridge, Cambridge, United Kingdom

    A central challenge in embryonic stem (ES) cell biology is to understand how to impose direction on primary lineage commitment. In basal culture conditions, the majority of ES cells convert asynchronously into neural cells. However, many cells resist differentiation and others adopt nonneural fates. Mosaic activation of the neural reporter Sox-green fluorescent protein suggests regulation by cell-cell interactions. We detected expression of Notch receptors and ligands in mouse ES cells and investigated the role of this pathway. Genetic manipulation to activate Notch constitutively does not alter the stem cell phenotype. However, upon withdrawal of self-renewal stimuli, differentiation is directed rapidly and exclusively into the neural lineage. Conversely, pharmacological or genetic interference with Notch signalling suppresses the neural fate choice. Notch promotion of neural commitment requires parallel signalling through the fibroblast growth factor receptor. Stromal cells expressing Notch ligand stimulate neural specification of human ES cells, indicating that this is a conserved pathway in pluripotent stem cells. These findings define an unexpected and decisive role for Notch in ES cell fate determination. Limiting activation of endogenous Notch results in heterogeneous lineage commitment. Manipulation of Notch signalling is therefore likely to be a key factor in taking command of ES cell lineage choice., 百拇医药