ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the murine auditory sensory epithelium.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
- Hearing restoration through hair cell regeneration: A review of recent advancements and current limitations.Hearing research · 2025Review
- Sox2 interacts with Atoh1 and Huwe1 loci to regulate Atoh1 transcription and stability during hair cell differentiation.PLoS genetics · 2025Article
- Review
- Prognostic significance of sex determining region Y-box 2, E-cadherin, and vimentin in esophageal squamous cell carcinoma.World journal of clinical cases · 2022Article
- Article
- Article
- GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27Scientific reports · 2021Article
- Tumor quiescence: elevating SOX2 in diverse tumor cell types downregulates a broad spectrum of the cell cycle machinery and inhibits tumor growth.BMC cancer · 2020Article
- The immune response after noise damage in the cochlea is characterized by a heterogeneous mix of adaptive and innate immune cells.Scientific reports · 2020Article
- LIN28B/Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Spatiotemporally controlled overexpression of cyclin D1 triggers generation of supernumerary cells in the postnatal mouse inner ear.Hearing research · 2020Article
- Hair cell regeneration from inner ear progenitors in the mammalian cochlea.American journal of stem cells · 2020Review
- Increased Type I and Decreased Type II Hair Cells after Deletion of Sox2 in the Developing Mouse Utricle.Neuroscience · 2019Article
- Sox2 dosage: A critical determinant in the functions of Sox2 in both normal and tumor cells.Journal of cellular physiology · 2019Review
- SOX2 is required for inner ear growth and cochlear nonsensory formation before sensory development.Development (Cambridge, England) · 2019Article
- Approaches for the study of epigenetic modifications in the inner ear and related tissues.Hearing research · 2019Review
- Multiple supporting cell subtypes are capable of spontaneous hair cell regeneration in the neonatal mouse cochlea.Development (Cambridge, England) · 2019Article
- ERBB2 signaling drives supporting cell proliferation in vitro and apparent supernumerary hair cell formation in vivo in the neonatal mouse cochlea.The European journal of neuroscience · 2018Article
- SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis.Development (Cambridge, England) · 2018Article
- Sox2 haploinsufficiency primes regeneration and Wnt responsiveness in the mouse cochlea.The Journal of clinical investigation · 2018Article
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
Sox2 plays critical roles in cell fate specification during development and in stem cell formation; however, its role in postmitotic cells is largely unknown. Sox2 is highly expressed in supporting cells (SCs) of the postnatal mammalian auditory sensory epithelium, which unlike non-mammalian vertebrates remains quiescent even after sensory hair cell damage. Here, we induced the ablation of Sox2, specifically in SCs at three different postnatal ages (neonatal, juvenile and adult) in mice. In neonatal mice, Sox2-null inner pillar cells (IPCs, a subtype of SCs) proliferated and generated daughter cells, while other SC subtypes remained quiescent. Furthermore, p27(Kip1), a cell cycle inhibitor, was absent in Sox2-null IPCs. Similarly, upon direct deletion of p27(Kip1), p27(Kip1)-null IPCs also proliferated but retained Sox2 expression. Interestingly, cell cycle control of IPCs by Sox2-mediated expression of p27(Kip1) gradually declined with age. In addition, deletion of Sox2 or p27(Kip1) did not cause a cell fate change. Finally, chromatin immunoprecipitation with Sox2 antibodies and luciferase reporter assays with the p27(Kip1) promoter support that Sox2 directly activates p27(Kip1) transcription in postmitotic IPCs. Hence, in contrast to the well known activity of Sox2 in promoting proliferation and cell fate determination, our data demonstrate that Sox2 plays a novel role as a key upstream regulator of p27(Kip1) to maintain the quiescent state of postmitotic IPCs. Our studies suggest that manipulating Sox2 or p27(Kip1) expression is an effective approach to inducing proliferation of neonatal auditory IPCs, an initial but necessary step toward restoring hearing in mammals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.