Role of Neurotrophins in the Generation of Spiral Ganglion Neuron-Like Cells from Embryonic Stem Cells

Spiral ganglion neurons (SGNs) are crucial for transferring auditory signals from cochlear sensory hair cells to the brainstem. However, SGNs are usually damaged in sensorineural hearing loss. Embryonic stem cells (ESCs) have been used to regenerate SGNs, but it is obscure whether ESC-derived neurons can fully resemble SGN subtype features. This study aimed to understand the effect of neurotrophins on the generation of SGN-like cells from ESCs and their subsequent subtype specification. This study utilized a stepwise neuronal generation approach to direct DsRed ESCs toward neural progenitors and eventually SGN-like cells. The derived SGN-like cells expressed multiple neuronal markers, including Tuj1, Map2, and NeuN, indicating maturity. Neurotrophins, including brain-derived neurotrophic factor, neutrotrophin-3, and nerve growth factor, seemed to regulate the generation of mature neurons from ESCs. In addition, derived neuron-like cells expressed the otic protein marker Gata3 and glutamatergic marker VGluT1, suggesting that they are SGN-like the glutamatergic cells. Significantly more SGN subtype marker-positive cells, including Pou4f1, calbindin, and calretinin-positive cells, were observed in the neurotrophin treatment groups. Overall, this study indicates the potential of SGN subtype generation from ESCs, which could be significant for cochlear implant therapy or stem cell-based replacement studies.