Molecular and physiological properties of regenerated juvenile and mature cochlea.

(A) In undamaged P7 (control) cochleae, CD44 is expressed in outer PCs, Claudius cells, and the LER. Representative images of the apical turn are shown. IPhC region is labeled by dashed lines. (B) In the P7 DT-treated Lgr5^DTR/+ cochlea, Sox2⁺ SCs in the PC/DC region have degenerated, with CD44⁺ Claudius cells and LER appearing grossly intact. (C, D) In both the undamaged and damaged P14 cochlea, Vglut3⁺ IHCs were surrounded by Na⁺/K⁺ ATPase α-1-expressing, Sox2⁺ IPhCs. (E) GLAST expression (membranous) of Sox2⁺ IPhCs in the P14 undamaged cochleae. IPhC region is outlined by dashed lines. (F) In the P14 damaged cochlea, all IPhCs expressed GLAST, and most were EdU-labeled. (G) In the P14 control cochlea, there were no EdU⁺ GLAST-tdTomato⁺ SCs in the inner sulcus. GLAST⁺ IPhCs were mostly GLAST-tdTomato⁺ but not EdU⁺. (H) In the P14 damage cochlea, many EdU⁺ GLAST-tdTomato⁺ GLAST⁺ IPhCs were detected. Orthogonal view shown in H’. (I, J) P21 DT-treated Lgr5^DTR/+ mice had higher ABRs and DPOAEs thresholds at all frequencies than controls. Data represent mean ± S.D. ***p < 0.001 (two-way ANOVA with Tukey’s multiple comparisons test). n = 7–8. See S1 Data for I and J. ABR, auditory brainstem response; DC, Deiters’ cell; DPOAE, distortion product otoacoustic emission; DT, diphtheria toxin; GER, greater epithelial ridge; IHC, inner hair cell; IPhC, inner phalangeal cell; LER, lesser epithelial ridge; OHC, outer hair cell; PC, pillar cell; SC, supporting cell; SPL, sound pressure level.

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