Single-Cell Transcriptome Analysis of Developing and Regenerating Spiral Ganglion Neurons

Abstract

The spiral ganglion neurons (SGNs) of the cochlea are essential for our ability to hear. SGN loss after exposure to ototoxic drugs or loud noise results in hearing loss. Pluripotent stem cell-derived and endogenous progenitor cell types have the potential to become SGNs and are cellular foundations for replacement therapies. Repurposing transcriptional regulatory networks to promote SGN differentiation from progenitor cells is a strategy for regeneration. Advances in the Fludigm C1 workflow or Drop-seq allow sequencing of single-cell transcriptomes to reveal variability between cells. During differentiation, the individual transcriptomes obtained from single-cell RNA-seq can be exploited to identify different cellular states. Pseudotemporal ordering of transcriptomes describes the differentiation trajectory, allows monitoring of transcriptional changes, and determines molecular barriers that prevent the progression of progenitors into SGNs. Analysis of single-cell transcriptomes will help develop novel strategies for guiding efficient SGN regeneration.