期刊
STEM CELLS
卷 30, 期 2, 页码 243-252出版社
WILEY
DOI: 10.1002/stem.775
关键词
Satellite cell; Notch; Quiescence; Rbpj; Muscle stem cell; Regeneration
资金
- Institut Pasteur
- Association Francaise contre le Myopathies
- Agence Nationale de la Recherche [ANR-06-BLAN-0039]
- EU
- Fondation pour la Recherche Medicale
- DIM STEM-Pole
- EMBO
- Agence Nationale de la Recherche (ANR) [ANR-06-BLAN-0039] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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