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Cell Stem Cell. 2018 Dec 6;23(6):859-868.e5. doi: 10.1016/j.stem.2018.09.017. Epub 2018 Nov 8.

Notch-Induced miR-708 Antagonizes Satellite Cell Migration and Maintains Quiescence.

Author information

1
Stem Cells and Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris 75015, France; CNRS UMR 3738, Institut Pasteur, Paris 75015, France; Sorbonne Universités, UPMC, University of Paris 06, IFD-ED 515, Paris 75252, France.
2
Bioimaging and Optics platform (BIOP), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
3
Stem Cells and Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris 75015, France; CNRS UMR 3738, Institut Pasteur, Paris 75015, France.
4
Stem Cells and Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris 75015, France; Dipartimento di Medicina Clinica e Chirurgica, Università degli Studi di Napoli Frederico II, 80131 Naples, Italy.
5
INSERM IMRB U955-E10, UPEC, ENVA, EFS, Créteil 94000, France.
6
UMR8203 "Vectorologie et Thérapeutiques Anticancéreuses," CNRS, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, France; Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, 94805 Villejuif, France.
7
Stem Cells and Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris 75015, France; CNRS UMR 3738, Institut Pasteur, Paris 75015, France. Electronic address: shahragim.tajbakhsh@pasteur.fr.

Abstract

Critical features of stem cells include anchoring within a niche and activation upon injury. Notch signaling maintains skeletal muscle satellite (stem) cell quiescence by inhibiting differentiation and inducing expression of extracellular components of the niche. However, the complete spectrum of how Notch safeguards quiescence is not well understood. Here, we perform Notch ChIP-sequencing and small RNA sequencing in satellite cells and identify the Notch-induced microRNA-708, which is a mirtron that is highly expressed in quiescent cells and sharply downregulated in activated cells. We employ in vivo and ex vivo functional studies, in addition to live imaging, to show that miR-708 regulates quiescence and self-renewal by antagonizing cell migration through targeting the transcripts of the focal-adhesion-associated protein Tensin3. Therefore, this study identifies a Notch-miR708-Tensin3 axis and suggests that Notch signaling can regulate satellite cell quiescence and transition to the activation state through dynamic regulation of the migratory machinery.

KEYWORDS:

focal adhesion; microRNA; migration; niche; quiescence; satellite cell; skeletal muscle stem cell; tensin3

PMID:
30416072
DOI:
10.1016/j.stem.2018.09.017
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