Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
Author
Udagawa, TomokatsuAtkinson, Patrick J
Milon, Beatrice
Abitbol, Julia M
Song, Yang
Sperber, Michal
Huarcaya Najarro, Elvis
Scheibinger, Mirko
Elkon, Ran
Hertzano, Ronna
Cheng, Alan G
Date
2021-11-10Journal
PLoS BiologyPublisher
Public Library of ScienceType
Article
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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.Identifier to cite or link to this item
http://hdl.handle.net/10713/17164ae974a485f413a2113503eed53cd6c53
10.1371/journal.pbio.3001445
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