Chondrolectin regulates the sublaminar localization and regenerative function of muscle satellite cells in mice

Skeletal muscle satellite cells (SCs) reside between the myofiber sarcolemma and basal lamina, where extracellular matrix (ECM) interactions maintain stemness and regenerative function. Here, we identify chondrolectin (CHODL), a type I transmembrane protein with a C-type lectin domain, as a critical regulator of SC biology. Single-cell RNA-seq analysis reveals that Chodl is highly enriched in quiescent SCs but downregulated in proliferating myoblasts. The conditional deletion of Chodl in embryonic myoblasts (Chodl ^MKO ) or adult SCs (Chodl ^PKO ) leaves muscle development intact yet delays injury-induced regeneration in young and aged mice. Chodl-deficient SCs exhibit reduced self-renewal and diminished proliferation, leading to defective myofiber repair. In silico network perturbation further predicts disrupted ECM-ligand interactions and Notch signaling, consistent with SC mislocalization outside the basal lamina and precocious activation in Chodl ^PKO muscle. Together, these findings establish CHODL as a determinant of SC niche localization and function, linking ECM interactions to muscle stem cell maintenance and repair.