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Nestin-expressing cells are mitotically active in the mammalian inner ear

Kalmanson, O;Takeda, H;Anderson, SR;Dondzillo, A;Gubbels, S;

Nestin expression is associated with pluripotency. Growing evidence suggests nestin is involved in hair cell development. The objective of this study was to investigate the morphology and role of nestin-expressing cells residing in the early postnatal murine inner ear. A lineage-tracing nestin reporter mouse line was used to further characterize these cells. Their cochleae and vestibular organs were immunostained and whole-mounted for cell counting. We found Nestin-expressing cells present in low numbers throughout the inner ear. Three morphotypes were observed: bipolar, unipolar, and globular. Mitotic activity was noted in nestin-expressing cells in the cochlea, utricle, saccule, and crista. Nestin-expressing cell characteristics were then observed after hair cell ablation in two mouse models. First, a reporter model demonstrated nestin expression in a significantly higher proportion of hair cells after hair cell ablation than in control cochleae. However, in a lineage tracing nestin reporter mouse, none of the new hair cells which repopulated the organ of Corti after hair cell ablation expressed nestin, nor did the nestin-expressing cells change in morphotype. In conclusion, Nestin-expressing cells were identified in the cochlea and vestibular organs. After hair cell ablation, nestin-expressing cells did not react to the insult. However, a small number of nestin-expressing cells in all inner ear tissues exhibited mitotic activity, supporting progenitor cell potential, though perhaps not involved in hair cell regeneration.