Cell Reports (Sep 2021)
A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma
- Beatrice Milon,
- Eldad D. Shulman,
- Kathy S. So,
- Christopher R. Cederroth,
- Erika L. Lipford,
- Michal Sperber,
- Jonathan B. Sellon,
- Heela Sarlus,
- Gabriela Pregernig,
- Benjamin Shuster,
- Yang Song,
- Sunayana Mitra,
- Joshua Orvis,
- Zachary Margulies,
- Yoko Ogawa,
- Christopher Shults,
- Didier A. Depireux,
- Adam T. Palermo,
- Barbara Canlon,
- Joe Burns,
- Ran Elkon,
- Ronna Hertzano
Affiliations
- Beatrice Milon
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Eldad D. Shulman
- Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Kathy S. So
- Decibel Therapeutics, Boston, MA 02215, USA
- Christopher R. Cederroth
- Laboratory of Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institute, 171 77 Stockholm, Sweden; Hearing Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
- Erika L. Lipford
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Michal Sperber
- Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Jonathan B. Sellon
- Decibel Therapeutics, Boston, MA 02215, USA
- Heela Sarlus
- Laboratory of Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institute, 171 77 Stockholm, Sweden; Applied Immunology & Immunotherapy, Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska University Hospital, 171 77 Stockholm, Sweden
- Gabriela Pregernig
- Decibel Therapeutics, Boston, MA 02215, USA
- Benjamin Shuster
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Yang Song
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Sunayana Mitra
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Joshua Orvis
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Zachary Margulies
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Yoko Ogawa
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Christopher Shults
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Didier A. Depireux
- Otolith Labs, Washington, DC 20009, USA
- Adam T. Palermo
- Decibel Therapeutics, Boston, MA 02215, USA
- Barbara Canlon
- Laboratory of Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institute, 171 77 Stockholm, Sweden
- Joe Burns
- Decibel Therapeutics, Boston, MA 02215, USA
- Ran Elkon
- Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Corresponding author
- Ronna Hertzano
- Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author
- Journal volume & issue
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Vol. 36,
no. 13
p. 109758
Abstract
Summary: Noise-induced hearing loss (NIHL) results from a complex interplay of damage to the sensory cells of the inner ear, dysfunction of its lateral wall, axonal retraction of type 1C spiral ganglion neurons, and activation of the immune response. We use RiboTag and single-cell RNA sequencing to survey the cell-type-specific molecular landscape of the mouse inner ear before and after noise trauma. We identify induction of the transcription factors STAT3 and IRF7 and immune-related genes across all cell-types. Yet, cell-type-specific transcriptomic changes dominate the response. The ATF3/ATF4 stress-response pathway is robustly induced in the type 1A noise-resilient neurons, potassium transport genes are downregulated in the lateral wall, mRNA metabolism genes are downregulated in outer hair cells, and deafness-associated genes are downregulated in most cell types. This transcriptomic resource is available via the Gene Expression Analysis Resource (gEAR; https://umgear.org/NIHL) and provides a blueprint for the rational development of drugs to prevent and treat NIHL.
