This research identifies Hypermethylated in cancer 1 (Hic1) as a specific marker for quiescent mesenchymal progenitors (MPs) within adult skeletal muscle. By using advanced lineage tracing and single-cell sequencing, the authors demonstrate that Hic1+ cells act as a critical signaling hub that orchestrates the stages of muscle regeneration. The study reveals that these progenitors are not a single group, but rather a collection of subpopulations—including fibro-adipogenic progenitors (FAPs) and tenogenic progenitors—with unique functional fates. Following an injury, these cells expand to provide essential immunomodulation and provisional matrix support before returning to a resting state. Notably, the research discovers a specialized cell type called the myotenocyte, which originates from Hic1+ progenitors to help form the interface between muscle and tendon. Ultimately, the findings establish that Hic1 is essential for maintaining the MP pool and ensuring successful tissue repair.

References:

• Scott RW, Arostegui M, Schweitzer R, Rossi FMV, Underhill TM. Hic1 Defines Quiescent Mesenchymal Progenitor Subpopulations with Distinct Functions and Fates in Skeletal Muscle Regeneration. Cell Stem Cell. 2019 Dec 5;25(6):797-813.e9. doi: 10.1016/j.stem.2019.11.004. PMID: 31809738; PMCID: PMC6941576.