Small-RNA sequencing identifies dynamic microRNA deregulation during skeletal muscle lineage progression

• Published in: Scientific reports 2018-03, Vol.8 (1), p.4208-13, Article 4208
• Main Authors: Castel, David, Baghdadi, Meryem B., Mella, Sébastien, Gayraud-Morel, Barbara, Marty, Virginie, Cavaillé, Jérôme, Antoniewski, Christophe, Tajbakhsh, Shahragim
• Format: Article
• Language: English
• Subjects: 13/1; 13/31; 38/39; 38/77; 38/90; 38/91; 45/100; 631/136/2441; 631/136/532/2118/2439; 631/208/212/2019; 631/337/384/331; 64/110; 64/60; Biochemistry, Molecular Biology; Cell self-renewal; Deregulation; Genomes; Homeostasis; Humanities and Social Sciences; Life Sciences; MicroRNAs; miRNA; multidisciplinary; Musculoskeletal system; Myogenesis; Preadipocyte factor 1; Satellite cells; Science; Science (multidisciplinary); Skeletal muscle; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-21991-w

Skeletal muscle satellite cells are quiescent adult resident stem cells that activate, proliferate and differentiate to generate myofibres following injury. They harbour a robust proliferation potential and self-renewing capacity enabling lifelong muscle regeneration. Although several classes of microRNAs were shown to regulate adult myogenesis, systematic examination of stage-specific microRNAs during lineage progression from the quiescent state is lacking. Here we provide a genome-wide assessment of the expression of small RNAs during the quiescence/activation transition and differentiation by RNA-sequencing. We show that the majority of small RNAs present in quiescent, activated and differentiated muscle cells belong to the microRNA class. Furthermore, by comparing expression in distinct cell states, we report a massive and dynamic regulation of microRNAs, both in numbers and amplitude, highlighting their pivotal role in regulation of quiescence, activation and differentiation. We also identify a number of microRNAs with reliable and specific expression in quiescence including several maternally-expressed miRNAs generated at the imprinted Dlk1-Dio3 locus. Unexpectedly, the majority of class-switching miRNAs are associated with the quiescence/activation transition suggesting a poised program that is actively repressed. These data constitute a key resource for functional analyses of miRNAs in skeletal myogenesis, and more broadly, in the regulation of stem cell self-renewal and tissue homeostasis.