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

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 fou...

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Autores principales:	Tomokatsu Udagawa, Patrick J Atkinson, Beatrice Milon, Julia M Abitbol, Yang Song, Michal Sperber, Elvis Huarcaya Najarro, Mirko Scheibinger, Ran Elkon, Ronna Hertzano, Alan G Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6257f12c990547c7b8b5062d341a46d0
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spelling	oai:doaj.org-article:6257f12c990547c7b8b5062d341a46d02021-12-02T19:54:33ZLineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.1544-91731545-788510.1371/journal.pbio.3001445https://doaj.org/article/6257f12c990547c7b8b5062d341a46d02021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001445https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Cochlear 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.Tomokatsu UdagawaPatrick J AtkinsonBeatrice MilonJulia M AbitbolYang SongMichal SperberElvis Huarcaya NajarroMirko ScheibingerRan ElkonRonna HertzanoAlan G ChengPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 11, p e3001445 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Tomokatsu Udagawa Patrick J Atkinson Beatrice Milon Julia M Abitbol Yang Song Michal Sperber Elvis Huarcaya Najarro Mirko Scheibinger Ran Elkon Ronna Hertzano Alan G Cheng Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
description	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.
format	article
author	Tomokatsu Udagawa Patrick J Atkinson Beatrice Milon Julia M Abitbol Yang Song Michal Sperber Elvis Huarcaya Najarro Mirko Scheibinger Ran Elkon Ronna Hertzano Alan G Cheng
author_facet	Tomokatsu Udagawa Patrick J Atkinson Beatrice Milon Julia M Abitbol Yang Song Michal Sperber Elvis Huarcaya Najarro Mirko Scheibinger Ran Elkon Ronna Hertzano Alan G Cheng
author_sort	Tomokatsu Udagawa
title	Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
title_short	Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
title_full	Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
title_fullStr	Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
title_full_unstemmed	Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
title_sort	lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6257f12c990547c7b8b5062d341a46d0
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Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.

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