Galectin and Myc enable cochlear progenitor expansion in vitro and in vivo

The neonatal cochlear epithelium harbors regenerative capacity, attributable to the transient greater epithelial ridge (GER). After injury, GER cells re-enter the cell cycle, migrate into the damaged organ of Corti, and differentiate into sensory or supporting cells in vivo; in culture, they proliferate to form inner ear organoids. The mechanisms underlying this competence remain unclear. Here, we generated organoids from mouse GER cells and performed single-cell transcriptomics at organoid initiation. Analysis revealed extracellular matrix reorganization with prominent involvement of galectins. Functional assays combining inhibition and overexpression demonstrated that galectin-1 and Myc are both necessary and sufficient for organoid growth. Moreover, Myc overexpression conferred organoid-forming capacity in post-neonatal cochlear epithelial cells after hearing onset, thereby extending the time window for regenerative competence. In vivo, organ of Corti ablation induced galectin-1 upregulation and GER proliferation, suppressed by galectin-1 blockade, establishing a model to rekindle proliferative potential in mature cochlear cells.