RT Journal Article
SR Electronic
T1 Regenerating motor neurons prime muscle stem cells for myogenesis by enhancing protein synthesis and mitochondrial bioenergetics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.24.113456
DO 10.1101/2020.05.24.113456
A1 Jeongmoon J. Choi
A1 Eun Jung Shin
A1 Woojin M. Han
A1 Shannon E. Anderson
A1 Mahir Mohiuddin
A1 Nan Hee Lee
A1 Thu Tran
A1 Shadi Nakhai
A1 Hyeonsoo Jeong
A1 Anna Shcherbina
A1 Gunjae Jeong
A1 Dong Gun Oh
A1 Laura D. Weinstock
A1 Sitara B. Sankar
A1 Molly E. Ogle
A1 Lida Katsimpardi
A1 Tata Nageswara Rao
A1 Levi Wood
A1 Carlos A. Aguilar
A1 Amy J. Wagers
A1 Young C. Jang
YR 2020
UL http://biorxiv.org/content/early/2020/05/26/2020.05.24.113456.abstract
AB 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.HighlightsMild 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.Competing Interest StatementThe authors have declared no competing interest.