Abstract
Cochlear supporting cells (SCs) are glia-like cells critical for hearing function. In the neonatal cochlea, the greater epithelial ridge (GER) is a mitotically quiescent and transient organ, which has been shown to nonmitotically regenerate SCs. Here, we ablated Lgr5+ SCs using Lgr5-DTR mice and found mitotic regeneration of SCs by GER cells in vivo. With lineage tracing, we show that the GER houses progenitor cells that robustly divide and migrate into the organ of Corti to replenish ablated SCs. Regenerated SCs display coordinated calcium transients, markers of the SC subtype inner phalangeal cells, and survive in the mature cochlea. Via RiboTag, RNA-sequencing, and gene clustering algorithms, we reveal 11 distinct gene clusters comprising markers of the quiescent and damaged GER, and damage-responsive genes driving cell migration and mitotic regeneration. Together, our study characterizes GER cells as mitotic progenitors with regenerative potential and unveils their quiescent and damaged translatomes.
Highlights
The cochlea requires both sensory hair cells (HCs) and nonsensory supporting cells (SCs) for sound reception
SC subtypes can be grouped as those residing in the medial (GER and inner phalangeal cells (IPhCs)) integrity number; SC, supporting cell; SPL, sound pressure level
In the damaged P4 cochleae, almost all Fabp7+ cells were ablated (Fig 3B and 3F), whereas many Fabp7+ tdTomato+ cells occupied the IPhC region at P7 (Fig 3Q-Q”“), indicating differentiation of greater epithelial ridge (GER)-derived cells into IPhCs. These results suggest that GLAST-Cre+ GER cells in the neonatal cochlea mitotically regenerated IPhCs
Summary
The cochlea requires both sensory hair cells (HCs) and nonsensory supporting cells (SCs) for sound reception. HCs are mechanoreceptors that convert sound into neural impulses [1,2], and SCs mediate spontaneous calcium transients, regulate glutamate uptake, govern HC innervation, provide trophic support for spiral ganglia neurons, and participate in intercellular metabolic coupling critical for organ maturation and maintenance [3,4,5,6,7,8].
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