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

Meryem Baghdadi (1, 2, 3) , Joao Firmino (4) , Kartik Soni (1) , Brendan Evano (1) , Daniela Di Girolamo (1, 5) , Philippos Mourikis (6, 7, 8) , David Castel (9, 10) , Shahragim Tajbakhsh (1)

1 Cellules Souches et Développement / Stem Cells and Development
2 SU - Sorbonne Université
3 SU FM - Sorbonne Université - Faculté de Médecine
4 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
5 University of Naples Federico II = Università degli studi di Napoli Federico II
6 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
7 ENVA - École nationale vétérinaire d'Alfort
8 IMRB - Institut Mondor de Recherche Biomédicale
9 UMR 8203 - Vectorologie et thérapeutiques anti-cancéreuses [Villejuif]
10 Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy]

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.

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

Domaines: Organisation et fonctions cellulaires [q-bio.SC]

Meryem Baghdadi, Joao Firmino, Kartik Soni, Brendan Evano, Daniela Di Girolamo, et al.. Notch-Induced miR-708 Antagonizes Satellite Cell Migration and Maintains Quiescence. Cell Stem Cell, 2018, 23 (6), pp.859-868.e5. ⟨10.1016/j.stem.2018.09.017⟩. ⟨hal-01990098⟩