A Critical Requirement for Notch Signaling in Maintenance of the Quiescent Skeletal Muscle Stem Cell State
A Critical Requirement for Notch Signaling in Maintenance of the Quiescent Skeletal Muscle Stem Cell State
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DOI：
10.1002/stem.775
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发表时间：
2012-02-01
期刊：
影响因子：
5.2
通讯作者：
Tajbakhsh, Shahragim
中科院分区：
文献类型：
--
作者：
Mourikis, Philippos;Sambasivan, Ramkumar;Tajbakhsh, Shahragim
Notch信号在后生动物几乎所有的组织和器官中都发挥着关键作用；然而，这一途径在成年静止干细胞中的调节作用的例子有限。我们对Notch通路的效应者进行了时间和本体论的评估，结果表明，在新分离的卫星细胞中活性最高，在第一次有丝分裂之前，意外地急剧下降，随后在增殖的卫星细胞来源的成肌细胞中也是如此。使用遗传工具有条件地在动态平衡期间消除典型的Notch信号，我们证明了卫星细胞自发分化并有助于肌纤维，从而导致干细胞库的严重枯竭。此外，尽管Rbpj功能的丧失会导致一些卫星细胞在融合前增殖，但引人注目的是，大多数突变细胞从静止状态到末端分化异常，没有通过S时相。本研究建立了Notch信号通路作为成体肌肉干细胞细胞静止的第一调节因子。干细胞，2012年；30：243252。
Notch signaling plays a key role in virtually all tissues and organs in metazoans; however, limited examples are available for the regulatory role of this pathway in adult quiescent stem cells. We performed a temporal and ontological assessment of effectors of the Notch pathway that indicated highest activity in freshly isolated satellite cells and, unexpectedly, a sharp decline before the first mitosis, and subsequently in proliferating, satellite cell-derived myoblasts. Using genetic tools to conditionally abrogate canonical Notch signaling during homeostasis, we demonstrate that satellite cells differentiate spontaneously and contribute to myofibers, thereby resulting in a severe depletion of the stem cell pool. Furthermore, whereas loss of Rbpj function provokes some satellite cells to proliferate before fusing, strikingly, the majority of mutant cells terminally differentiate unusually from the quiescent state, without passing through S-phase. This study establishes Notch signaling pathway as the first regulator of cellular quiescence in adult muscle stem cells. STEM CELLS 2012; 30:243252.