title: A critical requirement for notch signaling in maintenance of the quiescent skeletal muscle stem cell state.
abstract: 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.
authors: Stem Cells & Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578, Paris, France.
authors: Philippos
authors: P
authors: Mourikis
authors: Ramkumar
authors: R
authors: Sambasivan
authors: David
authors: D
authors: Castel
authors: Pierre
authors: P
authors: Rocheteau
authors: Valentina
authors: V
authors: Bizzarro
authors: Shahragim
authors: S
authors: Tajbakhsh
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D019070:Cell Lineage; D020869:Gene Expression Profiling; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D051880:Receptors, Notch / Q000378:metabolism*; D012038:Regeneration; D016196:S Phase; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch