Regenerating motor neurons prime muscle stem cells for myogenesis by enhancing protein synthesis and mitochondrial bioenergetics
Year: 2020
Type: preprint
Abstract: SUMMARY Throughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While the processes that control the coupling of neurotransmission and muscle contraction have been well characterized, little is known on the reciprocal crosstalk between neural cells and MuSCs within the muscle microenvironment. Here, we report that mild peripheral nerve injury enhances MuSC myogenic function and muscle regeneration by synergistically augmenting MuSC mitochondrial bioenergetics and upregulating anabolic protein synthesis pathways. We also demonstrate that chronic disruption or degeneration of neuromuscular synapses, such as in muscular dystrophy and biological aging, abolishes MuSC and motor neuron interactions, causing significant deficits in muscle regeneration following injury. These results underscore the importance of neuromuscular junction and neural network as an essential niche of MuSCs. Determining the significance of MuSC-nerve interactions and their functional outcomes, as well as the possibility of modulating these connections, have important implications for our understanding of neuromuscular disease pathology and development of therapeutic interventions. Highlights Mild peripheral nerve injury increases muscle stem cell bioavailability of healthy muscle. Nerve perturbation stimulates myogenesis by enhancing protein synthesis and mitochondrial metabolism in young, healthy muscle. Synergistic crosstalk within neuromuscular niche boosts muscle regeneration in young, healthy muscle. Positive influences from the neural network on muscle stem cells are abolished in pathological denervation manifested in dystrophic and aging muscle.
Authors: Jeongmoon J. Choi, Eun Jung Shin, Woojin M. Han, Shannon E. Anderson, Mahir Mohiuddin, Nan Hee Lee, Thu Tran, Shadi Nakhai, Hyeonsoo Jeong, Anna Shcherbina, Gunjae Jeong, Dong Gun Oh, Laura D. Weinstock, Sitara B. Sankar, Molly E. Ogle, Lida Katsimpardi, Tata Nageswara Rao, Levi Wood, Carlos A. Aguilar, Amy J. Wagers, Young C. Jang
Institutions: Georgia Institute of Technology, Emory University, The Wallace H. Coulter Department of Biomedical Engineering, Stanford University, Institut Pasteur, University of Bern, University Hospital of Bern, University of Michigan, Joslin Diabetes Center, Harvard University, Harvard Stem Cell Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3027191835