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 BurnsRan Elkon, Ronna Hertzano

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)109758
Number of pages1
JournalCell Reports
Volume36
Issue number13
DOIs
StatePublished - 28 Sep 2021

Keywords

  • ATF
  • IRF7
  • RiboTag
  • STAT3
  • cochlea
  • noise-induced hearing loss
  • scRNA-seq
  • spiral ganglion
  • transcriptomics

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