Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1194749 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here we demonstrate that in a mouse model for recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the neurons that innervate them. This includes genes regulating axonal pathfinding and synaptogenesis, two processes that are disrupted in the inner ear of the mutant mice. Similar defects are observed in mouse models for deafness caused by mutations in other genes with primary functions in hair cells. Gene therapy targeting hair cells restores hearing and inner ear circuitry in DFNB6 model mice. We conclude that hair cell function is crucial for the establishment of peripheral auditory circuitry. Treatment modalities for deafness thus need to consider restoration of the function of both hair cells and neurons, even when the primary defect occurs in hair cells.
2024-11-10 | GSE281207 | GEO
Project description:The mammalian inner ear subserves auditory and vestibular sensations via highly specialized cells and proteins. We show that sensory hair cells (HCs) employ hundreds of uniquely or highly expressed proteins for processes involved in transducing mechanical inputs, stimulating sensory neurons, and maintaining structure and function of these post-mitotic cells. Our proteomic analysis of purified HCs extends the existing HC transcriptome, revealing undetected gene products and isoform-specific protein expression. Comparison with mouse and human databases of genetic auditory/vestibular impairments confirms the critical role of the HC proteome for normal inner ear function, providing a cell-specific pool of candidates for novel, important HC genes. Several proteins identified exclusively in HCs by proteomics and by immunohistochemistry map to human genetic deafness loci, potentially representing new deafness genes.
2016-05-23 | MSV000079756 | MassIVE
Project description:We collected single cell transcriptome profiles of inner ear organoids from passage 2 (day 8) in expansion medium, differentiated day 5, and differentiated day 25. Cells from the three time points were divided into 5 distinct clusters by UMAP, indicating the presence of the basic cell types of the organ of Corti in cochlear organoid model. Deafness-related gene expression in differentiated day 25 organoid showed that the cell-type specificity related to genetic auditory disease was preserved in the organoids, and dynamic gene expression changes were observed along lineage trajectories form progenitors to mature cell types, similar to in vivo developmental process. These results showed that cochlea organoid can be used as a useful model for deciphering the effects of deafness gene mutations and understanding inner ear development.
2024-07-21 | GSE180553 | GEO
Project description:RNA-programmable deaminases, known as base editors (BEs), enable precise single base conversions on genomic DNA and hold great promise for therapeutic application in patients. Recent studies, however, have raised serious concern with regard to off-target effects, questioning translatability of BEs to the clinic. Here we analyze transcriptome- and genome-wide off-target effects following AAV-mediated delivery of cytosine base editors (CBEs) in vivo in an unbiased manner. We show that low expression of CBEs allows sufficient on-target editing to cure a disease phenotype with no increase in off-target effects compared to untreated controls. To further improve safety of in vivo base editing, we developed a lipid nanoparticle (LNP)-mediated delivery system to transiently express BEs. We reach up to 21% on-target editing with no detectable transcriptome- or genome-wide off-target effects, and are able to reverse the disease phenotype of a phenylketonuria mouse model. These results have important implications, underlining the feasibility of transient in vivo base editing for therapeutic use in patients.
2020-08-24 | GSE148349 | GEO