ArticlePLoS genetics2018
High-resolution transcriptional dissection of in vivo Atoh1-mediated hair cell conversion in mature cochleae identifies Isl1 as a co-reprogramming factor.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- 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
- Hearing restoration through hair cell regeneration: A review of recent advancements and current limitations.Hearing research · 2025Review
- Single-Cell Landscape of the Cochlea Revealed Cell-Type-Specific Diversification inBiomolecules · 2025Article
- The single-cell transcriptomic landscape of the topological differences in mammalian auditory receptors.Science China. Life sciences · 2024Article
- Advance and Application of Single-cell Transcriptomics in Auditory Research.Neuroscience bulletin · 2024Review
- In silico transcriptome screens identify epidermal growth factor receptor inhibitors as therapeutics for noise-induced hearing loss.Science advances · 2024Article
- Hair Cell Regeneration: From Animals to Humans.Clinical and experimental otorhinolaryngology · 2024Review
- Integrated scRNAseq analyses of mouse cochlear supporting cells reveal the involvement of Ezh2 in hair cell regeneration.Molecular biology reports · 2024Article
- Identification of multiple transcription factor genes potentially involved in the development of electrosensoryFrontiers in cell and developmental biology · 2024Article
- Accelerated Evolution Analysis Uncovers PKNOX2 as a Key Transcription Factor in the Mammalian Cochlea.Molecular biology and evolution · 2023Article
- Defining developmental trajectories of prosensory cells in human inner ear organoids at single-cell resolution.Development (Cambridge, England) · 2023Article
- Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform.Nature communications · 2023Article
- Single-cell transcriptomic atlas of mouse cochlear aging.Protein & cell · 2023Article
- Future Pharmacotherapy for Sensorineural Hearing Loss by Protection and Regeneration of Auditory Hair Cells.Pharmaceutics · 2023Review
- Stepwise fate conversion of supporting cells to sensory hair cells in the chick auditory epithelium.iScience · 2023Article
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- Precise detection of CRISPR-Cas9 editing in hair cells in the treatment of autosomal dominant hearing loss.Molecular therapy. Nucleic acids · 2022Article
- Profiling mouse cochlear cell maturation using 10× Genomics single-cell transcriptomics.Frontiers in cellular neuroscience · 2022Article
- Directed Differentiation of Human Pluripotent Stem Cells into Inner Ear Organoids.Methods in molecular biology (Clifton, N.J.) · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
In vivo direct conversion of differentiated cells holds promise for regenerative medicine; however, improving the conversion efficiency and producing functional target cells remain challenging. Ectopic Atoh1 expression in non-sensory supporting cells (SCs) in mouse cochleae induces their partial conversion to hair cells (HCs) at low efficiency. Here, we performed single-cell RNA sequencing of whole mouse sensory epithelia harvested at multiple time points after conditional overexpression of Atoh1. Pseudotemporal ordering revealed that converted HCs (cHCs) are present along a conversion continuum that correlates with both endogenous and exogenous Atoh1 expression. Bulk sequencing of isolated cell populations and single-cell qPCR confirmed 51 transcription factors, including Isl1, are differentially expressed among cHCs, SCs and HCs. In transgenic mice, co-overexpression of Atoh1 and Isl1 enhanced the HC conversion efficiency. Together, our study shows how high-resolution transcriptional profiling of direct cell conversion can identify co-reprogramming factors required for efficient conversion.
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