2012年9月18日 電 /生物谷BIOON/ --肌肉能提供干細(xì)胞來促進(jìn)肌肉的生長(zhǎng)和受傷肌肉的再生,但肌肉干細(xì)胞必須駐留在特殊的部位才能有助肌肉的生長(zhǎng)和修復(fù),。德爾柏林布呂克分子醫(yī)學(xué)中心(MDC)發(fā)育生物學(xué)家Dominique Bröhl和Carmen Birchmeier教授已經(jīng)闡明這些干細(xì)胞是如何定植于肌肉干細(xì)胞“巢穴”中的,。
肌肉干細(xì)胞也被稱為衛(wèi)星細(xì)胞,位于平滑肌細(xì)胞的質(zhì)膜和周圍基底層之間。可發(fā)育分化為成肌細(xì)胞,后者可互相融合成為多核的肌纖維,,形成骨骼肌最基本的結(jié)構(gòu)。
在本研究中,,Bröhl博士和教授Birchmeier表明,,小鼠的肌肉祖細(xì)胞缺乏Notch信號(hào)后,不能定植于干細(xì)胞“巢穴”,。相反,,肌肉祖細(xì)胞會(huì)定植于肌纖維之間的組織中。發(fā)育生物學(xué)家認(rèn)為,,這是肌肉弱化的原因,。干細(xì)胞定植于錯(cuò)誤的地方就不再像以前那樣擁有多種生物學(xué)功能,難以有助于肌肉生長(zhǎng),。
此外,,Notch信號(hào)通路在肌肉的發(fā)育過程中具有第二大功能。它可以通過抑制肌肉發(fā)育促進(jìn)因子MyoD防止干細(xì)胞分化成肌肉細(xì)胞,從而確保肌肉中總會(huì)存在能保存有修復(fù)和再生功能的干細(xì)胞“巢穴”,。這項(xiàng)工作對(duì)肌肉再生和肌肉無力的研究具有重大意義,。(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.