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    Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.

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    Author
    Udagawa, Tomokatsu
    Atkinson, Patrick J
    Milon, Beatrice
    Abitbol, Julia M
    Song, Yang
    Sperber, Michal
    Huarcaya Najarro, Elvis
    Scheibinger, Mirko
    Elkon, Ran
    Hertzano, Ronna
    Cheng, Alan G
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    Date
    2021-11-10
    Journal
    PLoS Biology
    Publisher
    Public Library of Science
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1371/journal.pbio.3001445
    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.
    Keyword
    cochlear supporting cells (SCs)
    mitotic regeneration
    translatomic analysis
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17164
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pbio.3001445
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