A Critical Requirement for Notch Signaling in Maintenance of the Quiescent Skeletal Muscle Stem Cell State (original) (raw)

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,

Stem Cells & Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578

, Paris,

France

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Stem Cells & Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578

, Paris,

France

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,

Stem Cells & Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578

, Paris,

France

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,

Stem Cells & Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578

, Paris,

France

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,

Department of Pharmaceutical and Biomedical Sciences, University of Salerno

, Fisciano, Salerno,

Italy

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Stem Cells & Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578

, Paris,

France

Correspondence: Shahragim Tajbakhsh, Prof., Stem Cells & Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578, 25 rue du Dr. Roux, 75105 Paris, France. Telephone: 33-1-40-61-35-20; Fax: 33-1-45-68-89-63; e-mail:

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Accepted:

25 October 2011

Published:

18 January 2012

Cite

Philippos Mourikis, Ramkumar Sambasivan, David Castel, Pierre Rocheteau, Valentina Bizzarro, Shahragim Tajbakhsh, A Critical Requirement for Notch Signaling in Maintenance of the Quiescent Skeletal Muscle Stem Cell State, Stem Cells, Volume 30, Issue 2, February 2012, Pages 243–252, https://doi.org/10.1002/stem.775
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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.

Disclosure of potential conflicts of interest is found at the end of this article.

Copyright © 2011 AlphaMed Press

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open\_access/funder\_policies/chorus/standard\_publication\_model)

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