A comprehensive transcriptomic atlas of the auditory organ at a molecular level has been created through an in-depth genomic study of the mouse cochlea by researchers at the Pasteur Institute in France.
“Single-cell transcriptomic profiling of the mouse cochlea” is the title of their paper. In A Chart Book for Designated Treatments,” distributed in the Procedures of the Public Foundation of Sciences, the group subtleties the production of a genomic data set for understanding the quality administrative organizations engaged with cochlear cell separation and development, which are fundamental for making designated medicines.
The gene expression profiles of more than 120,000 cells were analyzed in the study. The resulting cell atlas reveals cell-type-specific markers and provides information about nearly all cochlear cell types. Three already obscure cell types were found, two adding to the modiolus and one covering the scala vestibuli.
The two already obscure modiolus-related cells are transcriptomically distinct from other modiolus cell types, and the scientists figure they might be connected with the spongy design of the modiolar bone. Because known modiolar bone cells play distinct maturation roles in bone formation, they add that it is also possible that the two cells are one type of cell at distinct maturity stages.
The third cell type revelation was found lining the scala vestibuli, covering the epithelial cells of Reissner’s film, and is being called scala vestibuli line (SVB) cells. SVB cells expressed Eps8l2, Gjb2, Gjb6, Homer2, Coch, Clic5, Dcdc2a, Pou3f4, Col4a6, and Six1, all of which are responsible for the manifestation of various forms of deafness. Histological studies have never identified this cell tissue before.
The study also sheds light on the molecular basis of the tonotopic gradient of the biophysical characteristics of the basilar membrane, which is the inner ear’s primary mechanical component and essential for sound frequency analysis.
The basilar membrane functions as a frequency analyzer and generates a tonotopic map along the length of the cochlea, with high-frequency sounds being detected at the base and low-frequency sounds being detected at the apex.
The Emilin-2 protein, which is made by tympanic border cells and contributes to extracellular functions and tissue elasticity, is thought to be responsible for the basilar membrane’s stiffness gradient. It was discovered that Emilin2 mRNA is expressed in a gradient along the membrane, with a decrease in intensity from the base to the apex, which confirmed previous predictions.
Several transcription factors, including Gata6, Cux2, Nr1h3, Atoh8, and Atf3, followed a tonotopic intensity gradient in the opposite direction to Emilin2’s (Sp5, Foxf2, Dach1, Pbx3, Tbx1, Creb5, Osr1, Zic2, and Zic5), but Emilin2 was not the only one.
It was discovered that a variety of cochlear cell types express deafness genes. The expression patterns of 120 genes involved in isolated forms of deafness and 75 essential genes for cochlear development and function were examined by the researchers.
In some cochlear cell types, deafness genes had low expression levels and only increased in one type of cochlear cell at a particular stage. This manifestation of gene expression in deafness suggests that therapeutics should target specific combinations of cell types at specific times.
This brand-new single-cell sequenced atlas will come in handy for locating overlooked cochlear cells that are affected by specific deficits and may reveal unidentified causes of deafness. The reference can also be used in future research to decipher gene regulatory networks and cell signaling pathways for the development of safe and effective gene therapies.
More information: Philippe Jean et al, Single-cell transcriptomic profiling of the mouse cochlea: An atlas for targeted therapies, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2221744120
