Supporting cell characteristics in long-deafened aged mouse ears.
Significant sensory hair cell loss leads to irreversible hearing and balance deficits in humans and other mammals. Future therapeutic strategies to repair damaged mammalian auditory epithelium may involve inserting stem cells into the damaged epithelium, inducing non-sensory cells remaining in the epithelium to transdifferentiate into replacement hair cells via gene therapy, or applying growth factors. Little is currently known regarding the status and characteristics of the non-sensory cells that remain in the deafened auditory epithelium, yet this information is integral to the development of therapeutic treatments. A single high-dose injection of the aminoglycoside kanamycin coupled with a single injection of the loop diuretic furosemide was used to kill hair cells in adult mice, and the mice were examined 1 year after the drug insult. Outer hair cells are lost throughout the entire length of the cochlea and less than a third of the inner hair cells remain in the apical turn. Over 20% and 55% of apical organ of Corti support cells and spiral ganglion cells are lost, respectively. We examined the expression of several known support cell markers to investigate for possible support cell dedifferentiation in the damaged ears. The support cell markers investigated included the microtubule protein acetylated tubulin, the transcription factor Sox2, and the Notch signaling ligand Jagged1. Non-sensory epithelial cells remaining in the organ of Corti retain acetylated tubulin, Sox2 and Jagged1 expression, even when the epithelium has a monolayer-like appearance. These results suggest a lack of marked SC dedifferentiation in these aged and badly damaged ears.
Oesterle
Elizabeth C
EC
Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, WA, 98195, USA. oesterle@u.washington.edu
Campbell
Sean
S
D000375:Aging / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D002454:Cell Differentiation; D003638:Deafness / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000096:biosynthesis; D000072100:Jagged-1 Protein; D007612:Kanamycin / Q000008:administration & dosage / Q000009:adverse effects; D007760:Labyrinth Supporting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D055748:SOXB1 Transcription Factors / Q000032:analysis / Q000096:biosynthesis; D000072099:Serrate-Jagged Proteins; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D014404:Tubulin / Q000032:analysis / Q000096:biosynthesis
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D004232:Diuretics; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D055748:SOXB1 Transcription Factors; D000072099:Serrate-Jagged Proteins; C527783:Sox2 protein, mouse; D014404:Tubulin; D007612:Kanamycin; D005665:Furosemide