2012年9月18日 电 /生物谷BIOON/ --肌肉能提供干细胞来促进肌肉的生长和受伤肌肉的再生,但肌肉干细胞必须驻留在特殊的部位才能有助肌肉的生长和修复。德尔柏林布吕克分子医学中心(MDC)发育生物学家Dominique Bröhl和Carmen Birchmeier教授已经阐明这些干细胞是如何定植于肌肉干细胞“巢穴”中的。
肌肉干细胞也被称为卫星细胞,位于平滑肌细胞的质膜和周围基底层之间。可发育分化为成肌细胞,后者可互相融合成为多核的肌纤维,形成骨骼肌最基本的结构。
在本研究中,Bröhl博士和教授Birchmeier表明,小鼠的肌肉祖细胞缺乏Notch信号后,不能定植于干细胞“巢穴”。相反,肌肉祖细胞会定植于肌纤维之间的组织中。发育生物学家认为,这是肌肉弱化的原因。干细胞定植于错误的地方就不再像以前那样拥有多种生物学功能,难以有助于肌肉生长。
此外,Notch信号通路在肌肉的发育过程中具有第二大功能。它可以通过抑制肌肉发育促进因子MyoD防止干细胞分化成肌肉细胞,从而确保肌肉中总会存在能保存有修复和再生功能的干细胞“巢穴”。这项工作对肌肉再生和肌肉无力的研究具有重大意义。(生物谷:Bioon.com)
doi:10.1016/j.devcel.2012.07.014
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Colonization of the Satellite Cell Niche by Skeletal Muscle Progenitor Cells Depends on Notch Signals
Dominique Br?hl, Elena Vasyutina, Maciej T. Czajkowski, Joscha Griger, Claudia Rassek, Hans-Peter Rahn, Bettina Purfürst, Hagen Wende,
Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite cells deregulate the expression of basal lamina components and adhesion molecules like integrin α7, collagen XVIIIα1, Megf10, and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers.