snRNA-seq of the cochlear nucleus

The molecular mechanisms underlying the complex functions of the cochlear nucleus (CN) remain poorly understood, requiring a thorough characterization of cellular properties. We utilized single-nuclei RNA sequencing (snRNA-seq) and spatial enhanced resolution omics-sequencing (Stereo-seq) to generate a comprehensive celluar and molecular atlas of the CN and further defined various cell types and functionally spatial regions. Meanwhile, we identified the marker genes for the neurons and regions that were not previously reported. We further investigated the spatial distribution of different cell types and found that the neurons exhibited considerable regional specialization, which may account for the functional region formation. Transcriptome comparisons between normal and congenital hearing loss animal models indicated that bushy cell is the major cell type exhibiting transcriptomic response to auditory stimuli, and the expression pattern and dynamics of Spp1 were highlighted in the comparison, and similar pattern was also observed during CN development with the establishment of hearing. We functionally confirmed that Spp1 is required to maintain normal auditory processing by formatting the high conduction velocities axons from Spp1-/- mice. Taken together, our study provides an integrative spatially resolved cellular map of the CN and identifies critical cell types and genes involved in hearing loss and its treatment.