Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 10, 2021
- Source ID
- 10.1371/journal.pbio.3001445
Entities
People
- Alan G Cheng
- Beatrice Milon
- Elvis Huarcaya Najarro
- Julia M. Abitbol
- Michal Sperber
- Mirko Scheibinger
- Patrick J. Atkinson
- Ran Elkon
- Ronna Hertzano
- Tomokatsu Udagawa
- Yang Song
Organizations
- California Institute for Regenerative Medicine
- Garnett Passe and Rodney Williams Memorial Foundation
- Lucile Packard Foundation for Children's Health
- National Institute on Deafness and Other Communication Disorders
- National Institutes of Health
- Stanford University School of Medicine
- United States Department of Defense