ArticleeLife2022
Cellular reprogramming with ATOH1, GFI1, and POU4F3 implicate epigenetic changes and cell-cell signaling as obstacles to hair cell regeneration in mature mammals.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 78 citations in OpenAlex.
- CASZ1 regulates the maturation of outer hair cells and is required for hearing in mice.iScience · 2026Article
- BMP4 cocktail promotes utricular progenitor reprogramming and vestibular functional recovery in adult mice.Journal of advanced research · 2026Article
- Temporally segregated functions for Gfi1 in the development and maintenance of direction selectivity in the vertebrate retina.Current biology : CB · 2026Article
- Acbd7 is essential for preserving hair cell-mediated auditory and vestibular function.Experimental & molecular medicine · 2026Article
- Characteristics and Cell Lineage Tracing of Neurod1-Cre and Neurod1-iCreER Mice Targeting Cochlear Neurons.Neuroscience bulletin · 2026Article
- Galectin and Myc enable cochlear progenitor expansion in vitro and in vivo.bioRxiv : the preprint server for biology · 2026Article
- Multi-ancestry GWAS of age-related hearing loss identifies 140 loci and key cellular mechanisms.Nature communications · 2026Article
- Unraveling the core: hub genes bridging familial and sporadic Parkinson's disease.Journal of neurology · 2026Article
- Pou4f3 Deficiency Obstructs the Subtype Differentiation of Vestibular Hair Cells.Neuroscience bulletin · 2026Article
- Conditional knockout of Dkk3 drives Lgr5+ progenitor reprogramming into hair cells in the mouse cochlea.Theranostics · 2026Article
- Engineering exosomes in the treatment of sensorineural hearing loss: from basic research to clinical applications.Frontiers in molecular neuroscience · 2026Review
- Revealing heterogeneity and damage response in the adult human utricle.Nature communications · 2025Article
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- Ototoxicity-induced c-Fos activation underlies the regenerative capacity of the vestibular sensory epithelia.Cell communication and signaling : CCS · 2025Article
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- The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration.Nature communications · 2025Article
- prdm1a drives a fate switch between hair cells of different mechanosensory organs.Nature communications · 2025Article
- GDC: Integration of Multi-Omic and Phenotypic Resources to Unravel the Genetic Pathogenesis of Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- EDNRB2 regulates fate, migration, and maturation of hair cell precursors in regenerating avian auditory epithelium explants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Combined AAV-mediated specific Gjb2 expression restores hearing in DFNB1 mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed as a potential therapeutic strategy for hearing loss. ATOH1 expression in the developing cochlea can efficiently induce hair cell regeneration but the efficiency of hair cell reprogramming declines rapidly as the cochlea matures. We developed Cre-inducible mice to compare hair cell reprogramming with ATOH1 alone or in combination with two other hair cell transcription factors, GFI1 and POU4F3. In newborn mice, all transcription factor combinations tested produced large numbers of cells with the morphology of hair cells and rudimentary mechanotransduction properties. However, 1 week later, only a combination of ATOH1, GFI1 and POU4F3 could reprogram non-sensory cells of the cochlea to a hair cell fate, and these new cells were less mature than cells generated by reprogramming 1 week earlier. We used scRNA-seq and combined scRNA-seq and ATAC-seq to suggest at least two impediments to hair cell reprogramming in older animals. First, hair cell gene loci become less epigenetically accessible in non-sensory cells of the cochlea with increasing age. Second, signaling from hair cells to supporting cells, including Notch signaling, can prevent reprogramming of many supporting cells to hair cells, even with three hair cell transcription factors. Our results shed light on the molecular barriers that must be overcome to promote hair cell regeneration in the adult cochlea.
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