Journal Article

Retinoic acid maintains human skeletal muscle progenitor cells in an immature state

Vernus, Barbara, Mercier, Jacques, Notarnicola, Cécile, Carnac, Gilles, El Haddad, Marina, Evano, Brendan, Blaquière, Marine, Tajbakhsh, Shahragim, Bonnieu, Anne, El Khatib, Nour, Hugon, Gérald

2017

Overview

Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor. Conversely, pharmacologic or genetic inactivation of endogenous retinoic-acid receptors improved myoblast differentiation. Retinoic acid inhibits the expression of early and late muscle differentiation markers and enhances the expression of myogenic specification genes, such as PAX7 and PAX3 . These results suggest that the retinoic-acid-signalling pathway might maintain myoblasts in an undifferentiated/immature stage. To determine the relevance of these observations, we characterised the retinoic-acid-signalling pathways in freshly isolated satellite cells in mice and in siMYOD immature human myoblasts. Our analysis reveals that the immature state of muscle progenitors is correlated with high expression of several genes of the retinoic-acid-signalling pathway both in mice and in human. Taken together, our data provide evidences for an important role of the retinoic-acid-signalling pathway in the regulation of the immature state of muscle progenitors.

• Publisher: Springer International Publishing,Springer Nature B.V,Springer Verlag
• Subject: Adult / Animals / Biochemistry / Biomedical and Life Sciences / Biomedicine / Cell Biology / Cell death / Cell Differentiation / Cell survival / Cells (biology) / Cells, Cultured / Cellular biology / Cytotoxic agents / Cytotoxicity / death / Differentiation / Gene expression / Gene Expression Regulation, Developmental / Genes / Human health and pathology / Humans / immatures / Inactivation / Life Sciences / Male / Metabolites / Mice / Muscle Development / Muscles / Musculoskeletal diseases / Myoblasts / Myoblasts - cytology / Myoblasts - metabolism / MyoD Protein - genetics / MyoD Protein - metabolism / Original / Original Article / Pax3 protein / Progenitor cells / Receptors / Receptors, Retinoic Acid - metabolism / Retinoic acid / retinoic acid receptors / RNA Interference / Satellite cells / Signal Transduction / Skeletal muscle / Tissues and Organs / Tretinoin - metabolism