Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids.

Stem Cell Reports

Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address:

Published: July 2019

AI Article Synopsis

  • Mutations in the TMPRSS3 gene are linked to hearing loss, but the exact mechanisms remain unclear.
  • Research using stem cell-derived inner ear organoids and single-cell RNA sequencing revealed that defective TMPRSS3 leads to hair cell death (apoptosis) without affecting their development.
  • Observations indicated that hair cells lacking TMPRSS3 have fewer BK channels and altered expression of calcium ion-binding proteins, pointing to disrupted cellular balance, while the study provides a useful model for investigating inner ear disorders.

Article Abstract

Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626982PMC
http://dx.doi.org/10.1016/j.stemcr.2019.05.014DOI Listing

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