An immortalized cochlear spiral ganglion neuronal cell line: a promising tool for hearing loss study

Mammalian spiral ganglion neurons (SGNs) in the cochlear are crucial for auditory signal processing. The degeneration and loss of SGNs leads to irreversible sensorineural hearing loss (SNHL) due to their limited regenerative capacity. However, the anatomical complexity and restricted accessibility of SGNs pose challenges for their research. In this study, we established a conditionally immortalized cell line, Shandong Institute of Otorhinolaryngology-spiral ganglion neuron 1 (SIO-SGN1), by introducing SV40 large T antigen into neonatal mouse SGNs. SIO-SGN1 cells showed robust proliferative capability and maintained high viability over 20 passages. They exhibited contact inhibition and expressed neuronal-specific markers but not glial or hair cell markers. Transcriptome analysis revealed that the transcriptomic profile of SIO-SGN1 cells closely resembles that of primary SGNs at embryonic day 15.5 and postnatal day 1. These cells highly expressed genes related to neuron development, axon guidance, synapse formation, and stemness. Treatment with the ototoxic drugs cisplatin or ouabain caused significant cell loss and damage in SIO-SGN1 cells, which was consistent with the drug responses observed in cultured primary SGNs. Collectively, our findings suggest that SIO-SGN1 cells serve as a promising in vitro model for screening ototoxic and otoprotective drugs, and investigating the molecular mechanisms underlying ototoxic drug-induced SGN loss and hearing impairment.