Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them ‘guide’ cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the form-ing myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regen-eration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers.

Guide cells support muscle regeneration and affect neuro-muscular junction organization / Ronzoni, Fl; Giarratana, N; Crippa, S; Quattrocelli, M; Cassano, M; Ceccarelli, G; Benedetti, L; Van Herck, J; Cusella De Angelis, Mg; Vitale, M; Galli, D; Sampaolesi, M.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:4(2021), pp. 1-16. [10.3390/ijms22041939]

Guide cells support muscle regeneration and affect neuro-muscular junction organization

Vitale M;
2021-01-01

Abstract

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them ‘guide’ cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the form-ing myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regen-eration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers.
2021
Animals
Antigens
CD34
Cell Differentiation
Endothelial Cells
Endothelium
Vascular
Hyaluronan Receptors
Mice
Mice
Inbred C57BL
Mice
Nude
Muscle Development
Muscle Fibers
Skeletal
Muscle
Skeletal
Muscle
Smooth
Vascular
Neural Cell Adhesion Molecules
Neuromuscular Junction
Regeneration
RNA-Seq
Single-Cell Analysis
SOXB1 Transcription Factors
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/154069
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