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

  • bioRxiv. 2026 Jun 7:2026.06.03.729765. doi: 10.64898/2026.06.03.729765.
Marie Kubota  1  2  3 ,  Julia M Abitbol  1  4 ,  Paul K Lee  1  2  5 ,  Maggie S Matern  1  2  6 ,  Sonia Bustos Barocio  7 ,  Taha A Jan  8 ,  Alan G Cheng  1 ,  Stefan Heller  1  2
Affiliations
  • 1. Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3. Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77551, USA.
  • 4. Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, M4N 3M5, Canada.
  • 5. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 6. Department of Natural Sciences, Merrimack College, North Andover, MA 01845, USA.
  • 7. Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 8. Department of Otolaryngology-Head and Neck Surgery, Epithelial Biology Center, Vanderbilt Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
PMID: 42282633 DOI: 10.64898/2026.06.03.729765
Abstract

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.

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