Regenerated hair cells in the neonatal cochlea are innervated and the majority co-express markers of both inner and outer hair cells.

After a damaging insult, hair cells can spontaneously regenerate from cochlear supporting cells within the first week of life. While the regenerated cells express several markers of immature hair cells and have stereocilia bundles, their capacity to differentiate into inner or outer hair cells, and ability to form new synaptic connections has not been well-described. In addition, while multiple supporting cell subtypes have been implicated as the source of the regenerated hair cells, it is unclear if certain subtypes have a greater propensity to form one hair cell type over another. To investigate this, we used two CreER mouse models to fate-map either the supporting cells located near the inner hair cells (inner phalangeal and border cells) or outer hair cells (Deiters', inner pillar, and outer pillar cells) along with immunostaining for markers that specify the two hair cell types. We found that supporting cells fate-mapped by both CreER lines responded early to hair cell damage by expressing Atoh1, and are capable of producing regenerated hair cells that express terminal differentiation markers of both inner and outer hair cells. The majority of regenerated hair cells were innervated by neuronal fibers and contained synapses. Unexpectedly, we also found that the majority of the laterally positioned regenerated hair cells aberrantly expressed both the outer hair cell gene, oncomodulin, and the inner hair cell gene, vesicular glutamate transporter 3 (VGlut3). While this work demonstrates that regenerated cells can express markers of both inner and outer hair cells after damage, VGlut3 expression appears to lack the tight control present during embryogenesis, which leads to its inappropriate expression in regenerated cells.

Socioeconomic Status and Rurality Among Patients With Head and Neck Cancer.

OBJECTIVE: Describe the relationship among rurality, socioeconomic status (SES), and patient/tumor characteristics in patients presenting with head and neck cancer. STUDY DESIGN: Retrospective single-institution study. SETTING: Academic tertiary-level medical center. METHODS: Patients with head and neck cancer presenting between 2011 and 2015 were included. Stage at presentation, insurance status, and demographic characteristics were collected. Rurality was measured through Rural-Urban Continuum Codes. SES was measured by SES index scores of the Agency for Healthcare Research and Quality, which incorporate multiple components of SES. Associations among rurality, SES, and patient/tumor characteristics were assessed with univariate and multivariable statistics. All P values were calculated via 2-sided hypotheses. The threshold for statistical significance was set at P < .05. Statistical analyses were conducted with Stata/SE 14 (StataCorp). RESULTS: The study included 266 patients diagnosed with head and neck cancer between 2011 and 2015. Rural residence was associated with lower SES (P < .001). T and N stages were associated with rurality (P = .036 and .050, respectively). Higher educational status was associated with oropharyngeal cancer (P = .005). CONCLUSIONS: Rurality and SES have distinct impacts on patients with head and neck cancer. Specifically, rurality is associated with tumor stage among patients with head and neck cancer. Knowledge of disparities among patients with rural residency may help target interventions to facilitate earlier diagnosis.