TY - JOUR
T1 - Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration
AU - Udagawa, Tomokatsu
AU - Atkinson, Patrick J.
AU - Milon, Beatrice
AU - Abitbol, Julia M.
AU - Song, Yang
AU - Sperber, Michal
AU - Najarro, Elvis Huarcaya
AU - Scheibinger, Mirko
AU - Elkon, Ran
AU - Hertzano, Ronna
AU - Cheng, Alan G.
N1 - Publisher Copyright:
© 2021 Udagawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/11
Y1 - 2021/11
N2 - Cochlear supporting cell (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 damageresponsive 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.
AB - Cochlear supporting cell (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 damageresponsive 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.
UR - http://www.scopus.com/inward/record.url?scp=85119934358&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.3001445
DO - 10.1371/journal.pbio.3001445
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C2 - 34758021
AN - SCOPUS:85119934358
SN - 1544-9173
VL - 19
JO - PLoS Biology
JF - PLoS Biology
IS - 11
M1 - e3001445
ER -
