biostudies-literatureUdagawa TNCATS NIH HHSGarnett Passe and Rodney Williams Memorial Foundation Research Training GrantLucile Packard Foundation for Children’s HealthNIDCD NIH HHSU.S. Department of DefenseNational Institute on Deafness and Other Communication DisordersSchool of Medicine, Stanford UniversityAkiko Yamazaki and Jerry Yang Faculty Scholar Fund and Yu and Oberndorf familiesNational Institutes of HealthCalifornia Institute for Regenerative MedicineChild Health Research Institute of Stanford Universitye3001445https://www.ebi.ac.uk/biostudies/studies/S-EPMC8608324biostudies-literatureUnknown19(11)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 daPLoS biologyLineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.PMC8608324UL1 TR001085UL1 TR003142K08 DC011043RO1DC13910R01 DC001910U01 DC013817R01 DC019370RN3-06529K08DC011043R01 DC013817RO1DC01910MR130316MR130240R01DC013817R01 DC013910Dean's postdoctoral fellowshipNIH-NCATS-CTSA UL1 TR001085Huarcaya Najarro ECheng AGAtkinson PJMilon BHertzano RSperber MElkon RScheibinger MUdagawa TAbitbol JMSong YfalseLineage-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 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 da2021-01-01T00:00:00Z2021 Nov2026-05-09T20:20:51.178Z2022-02-11T13:12:38.961ZS-EPMC86083243475802110.1371/journal.pbio.3001445