Why the study?
Recent advances prompted reexamination of the origin and direct contribution of non-myogenic interstitial populations to the myogenic lineage during muscle growth and repair.
This review highlights growing evidence that non-myogenic interstitial cells actively contribute to myogenesis, challenging the traditional view that satellite cells are the sole contributors to muscle fiber formation.
PAX3+/PAX7+ progenitors and interstitial cells support muscle regeneration; leaves open clinical translation to cardiovascular contexts.
The developmental origin of skeletal muscle cell lineages has been extensively studied in the last 50 years. PAX3 + /PAX7 + myogenic progenitors are the foundation for skeletal muscle development and give rise to muscle satellite cells that support skeletal muscle postnatal growth, homeostasis and regeneration. Research into muscle connective tissue interstitial cells established their supportive role in muscle patterning during development and regeneration. With recent advances in mouse genetic lineage tracing, single cell transcriptomics and specific antibodies, the origin and the contribution of non-myogenic interstitial populations to the myogenic lineage have been reexamined. Growing evidence suggests that subpopulations of muscle interstitial cells actively contribute to myogenesis and fuse with myofibers during development, postnatal growth, and regeneration. In this review, we focus on the recent research advances that highlighted the direct contribution of interstitial cells, particularly connective tissue cells, to skeletal muscle growth and repair. We stress the importance of further investigating the mechanisms by which interstitial cells contribute to a myogenic fate in both physiological and pathological conditions.
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Issa et al. (2026) studied this question.
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