Abstract
Greater epithelial ridge cells, a transient neonatal cell group in the cochlear duct, which plays a crucial role in the functional maturation of hair cell, structural development of tectorial membrane, and refinement of audio localization before hearing. Greater epithelial ridge cells are methodologically homogeneous, while whether different cell subtypes are existence in this intriguing region and the degeneration mechanism during postnatal cochlear development are poorly understood. In the present study, single-cell RNA sequencing was performed on the cochlear duct of postnatal rats at day 1 (P1) and day 7 (P7) to identify subsets of greater epithelial ridge cell and progression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to examine genes enriched biological processes in these clusters. We identified a total of 26 clusters at P1 and P7 rats and found that the cell number of five cell clusters decreased significantly, while four clusters had similar gene expression patterns and biological properties. The genes of these four cell populations were mainly enriched in Ribosome and P13K-Akt signal pathway. Among them, Rps16, Rpsa, Col4a2, Col6a2, Ctsk, and Jun are particularly interesting as their expression might contribute to the greater epithelial ridge cells degeneration. In conclusion, our study provides an important reference resource of greater epithelial ridge cells landscape and mechanism insights for further understanding greater epithelial ridge cells degeneration during postnatal rat cochlear development.
Highlights
Mammalian hearing is dependent on the normal development of the cochlea, which includes the development of hair cells and supporting cells
We further reduced the dimensionality of all 25139 cells using Seurat and used t-distributed stochastic neighbor embedding (t-SNE) to project the cells into 2D space (Satija et al, 2015), the steps include: (1) Using the Log normalize method of the “Normalization” function of the Seurat software to calculate the expression value of genes; (2) PCA (Principal component analysis) analysis was performed using the normalized expression value, Within all the PCs, the top 10 PCs were used to do clustering and t-SNE analysis; (3) To find clusters, selecting weighted Shared Nearest Neighbor (SNN) graph-based clustering method
The cochlear duct cells comprise a highly diverse cellular mosaic that includes an undefined number of supporting cell (SC) types, two different types of mechanosensory hair cells (HCs), and unknown cell types in Kölliker’s organ (KO)
Summary
Mammalian hearing is dependent on the normal development of the cochlea, which includes the development of hair cells and supporting cells. The mammalian inner ear contains the vestibular sensory epithelium that perceives various accelerations and the auditory epithelia that perceive sound stimuli (Kelley, 2007). The auditory epithelium contains two main cell types: supporting cells and hair cells with greatly different anatomical and physiological characteristics (Scheffer et al, 2015). Hair cells continuously receive various stimuli from supporting cells and the outside world through unique receptors during their growth and development. These include the G-protein coupled P2Y receptors that activate phospholipase C (PLC) dependent production of inositor triphosphate (IP3) and release of intracellular ionized calcium (Ca2+) from intracellular stores (Forsythe, 2007; Tritsch et al, 2007). Glutamate release from IHCs activates type I spiral neurons (SGNs) to generate action potentials, thereby mimicking in the prehearing cochlea the mechanical-electrical signal transduction effect triggered by acoustic waves transmitted via the external auditory canal (Tritsch and Bergles, 2010; Mammano and Bortolozzi, 2018; Ceriani et al, 2019), resulting in an increase in the frequency of spontaneous action potential release from IHCs and promoting the functional maturation of IHCs (Flores-Otero et al, 2007; Tritsch and Bergles, 2010; Dayaratne et al, 2014)
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