Quantitative Study on Self-Renewal of Vestibular Hair Cells in a Sox9-CreER Mouse Line

Abstract

Background: Hair cells (HCs) are the mechanoreceptors for body position changes. Studies have suggested that HCs in mammals are terminally differentiated cells, which cannot regenerate after injury. Vestibular organs can generate new HCs, albeit in limited numbers. Methods: We carried out a study to analyse quantitatively and qualitatively spontaneous regeneration of vestibular HCs at different life stages. A Sox9-CreER transgenic mouse model specifically labelled with vestibular SCs was established. The proliferating cells, proliferative SCs, proliferative regenerated HCs and trans-differentiated HCs in mouse utricles of different ages were counted and analysed. Findings: We report that, from P1 to P30, the number of HCs in mouse utricles increased while the number of SCs decreased. The proliferation of SCs could be maintained until two weeks after birth. In the first week after birth, more than 30% of the total HCs were born. With an increase of age, the efficiency of HC regeneration decreased. In the adult stage, approximately 9% of new HCs still existed. Both types of HCs can be regenerated. Regenerated traced HCs are characterized by short, long, and absent bundles. Interpretation: Sox9 specifically labelled the vestibular SCs. HCs in the mouse vestibular apparatus undergo low-level turnover even in adulthood. These findings expand our understanding of sensorineural plasticity in adult vestibular organs in mammals after birth. Funding Statement: This work was supported by the National Natural Science Foundation of China (Nos. 81470687). Declaration of Interests: No authors have any professional or financial affiliations that may be regarded as a conflict of interest. Ethics Approval Statement: All animal procedures were approved by the Animal Care and Use Committee of Fudan University and were consistent with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.