The loss of primary auditory neurons (PANs) leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency and these iNs expressed several key markers of neuron identity. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, demonstrating that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs. SOURCE: Yutaka Amemiya (yamemiya@sri.utoronto.ca) - Genomics Core Facility Sunnybrook Research Institute

Pluto Bioinformatics

GSE107461: Direct reprogramming of spiral ganglion non-neuronal cells into neurons: Towards ameliorating sensorineural hearing loss by gene therapy