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

Autor: Michal Sperber, Elvis Huarcaya Najarro, Mirko Scheibinger, Ran Elkon, Tomokatsu Udagawa, Beatrice Milon, Julia M. Abitbol, Ronna Hertzano, Yang Song, Patrick J. Atkinson, Alan G. Cheng
Rok vydání: 2021
Předmět:
Bacterial Diseases
Pulmonology
Gene Expression
Toxicology
Pathology and Laboratory Medicine
Epithelium
Receptors
G-Protein-Coupled
Mice
Medical Conditions
Animal Cells
Gene expression
Medicine and Health Sciences
Toxins
Biology (General)
Organ of Corti
Inner Hair Cells
Neurons
integumentary system
Stem Cells
General Neuroscience
LGR5
Cell Differentiation
Diphtheria
Cell migration
Deiter's Cells
Cochlea
Precipitation Techniques
Cell biology
Infectious Diseases
medicine.anatomical_structure
Multigene Family
Inner Ear
Anatomy
Cellular Types
General Agricultural and Biological Sciences
tissues
Research Article
Cell Survival
QH301-705.5
Toxic Agents
Mitosis
Biology
Research and Analysis Methods
General Biochemistry
Genetics and Molecular Biology
Respiratory Disorders
Genetics
Upper Respiratory Tract Infections
medicine
Animals
Regeneration
Immunoprecipitation
Cell Lineage
Progenitor cell
Genetic Association Studies
Integrases
General Immunology and Microbiology
Regeneration (biology)
fungi
Labyrinth Supporting Cells
Biology and Life Sciences
Afferent Neurons
Epithelial Cells
Cell Biology
Biological Tissue
Gene Expression Regulation
nervous system
Ears
Protein Biosynthesis
Cellular Neuroscience
Respiratory Infections
Head
Neuroscience
Zdroj: PLoS Biology, Vol 19, Iss 11, p e3001445 (2021)
PLoS Biology
ISSN: 1545-7885
Popis: 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.
Cochlear supporting cells are glia-like cells essential for hearing. Genetic ablation of Lgr5+ supporting cells reveals a population of damage inducible, mitotically activated progenitors in the greater epithelial ridge, which can divide and migrate into the organ of Corti to replenish ablated supporting cells. Translatomic analyses provide insights into the genes that may regulate this regenerative potential.
Databáze: OpenAIRE
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