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Publication : The single-cell transcriptomic landscape of the topological differences in mammalian auditory receptors.

First Author  Ma X Year  2024
Journal  Sci China Life Sci Volume  67
Issue  11 Pages  2398-2410
PubMed ID  39083201 Mgi Jnum  J:357530
Mgi Id  MGI:7764129 Doi  10.1007/s11427-024-2672-1
Citation  Ma X, et al. (2024) The single-cell transcriptomic landscape of the topological differences in mammalian auditory receptors. Sci China Life Sci 67(11):2398-2410
abstractText  Mammalian hair cells (HCs) are arranged spirally along the cochlear axis and correspond to different frequency ranges. Serving as primary sound detectors, HCs spatially segregate component frequencies into a topographical map. HCs display significant diversity in anatomical and physiological characteristics, yet little is known about the organization of the cochleotopic map of HCs or the molecules involved in this process. Using single-cell RNA sequencing, we determined the distinct molecular profiles of inner hair cells and outer hair cells, and we identified numerous position-dependent genes that were expressed as gradients. Newly identified genes such as Ptn, Rxra, and Nfe2l2 were found to be associated with tonotopy. We employed the SCENIC algorithm to predict the transcription factors that potentially shape these tonotopic gradients. Furthermore, we confirmed that Nfe2l2, a tonotopy-related transcription factor, is critical in mice for sensing low-to-medium sound frequencies in vivo. the analysis of cell-cell communication revealed potential receptor-ligand networks linking inner hair cells to spiral ganglion neurons, including pathways such as BDNF-Ntrk and PTN-Scd4, which likely play essential roles in tonotopic maintenance. Overall, these findings suggest that molecular gradients serve as the organizing principle for maintaining the selection of sound frequencies by HCs.
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