Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea.

Summary

Follow-up to the 2013 Notch-inhibition work, this study used lineage tracing to pin down exactly which supporting cells give rise to new hair cells after damage: Lgr5-expressing inner pillar cells and third Deiters' cells. New hair cells were predominantly outer hair cells, and pharmacological Notch inhibition substantially increased how many were generated, reinforcing Lgr5+ cells as a defined target population for regeneration strategies rather than the supporting-cell pool as a whole.

Key findings

• Lineage tracing in the postnatal mouse cochlea showed new hair cells after damage arise specifically from Lgr5-expressing inner pillar cells and third Deiters' cells.
• The new hair cells generated were predominantly outer hair cells.
• Pharmacological Notch inhibition significantly increased the rate of new hair cell generation from this Lgr5+ population.
• Narrows the regeneration target from 'supporting cells' broadly to a defined, marker-identifiable subpopulation.