Multimodal profiling reveals a Notch-responsive regenerative subpopulation of cochlear supporting cells [2]

A major cause of hearing loss arises from the irreversible loss of sensory hair cells (HCs) in the cochlea. While supporting cells (SCs) have a latent ability to trans-differentiate into HCs, this regenerative potential is rapidly lost after development.

Using live imaging and single-cell multiomics of cochlear explants, we uncovered the cellular and molecular heterogeneity underlying the limited regenerative capacity of the neonatal mouse cochlea. Notch repression broadly silenced key SC genes, yet only a rare subpopulation of Deiters cells (DC), termed responsive DCs, initiated the trans-differentiation into HC fate. These cells underwent coordinated transcriptional and enhancer remodeling, linking epigenetic priming with morphological plasticity, while other SCs remained refractory despite robust Notch targets downregulation.