Robust mitotic regeneration by hidden progenitors after ablation of Lgr5+ cochlear cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE135728 | GEO | 2020/08/01
REPOSITORIES: GEO
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Project description:Robust mitotic regeneration by hidden progenitors after ablation of Lgr5+ cochlear cells
| PRJNA559868 | ENA
Project description:We sequenced the total RNA of cells from inner ear organoids generated by EFI,EFI-4C and EFI-CL expansion strategies. Transcriptional profiles revealed that CHIR and LPA significantly increased proliferative potency and contributed to the stemness maintenance. We further compared the gene expression profiles among the sorted Lgr5+ CPCs, the primary organoids of passage (P)0, the P4 organoids, and the sorted E-cadherin+ sensory epithelial cells. Inner ear organoids recapitulated genetic characteristics of auditory epithelium rather than Lgr5+ progenitors alone. Differential gene analysis of cells from primary organoids and organoids at fourth passage indicated stable transcriptional profiles among passages, which confirmed the reliability and authenticity of cochlear organoids for modeling the properties of the cochlea.
2024-07-21 | GSE180552 | GEO
Project description:Transcriptome analysis of human inner ear tissue Hearing loss is common and caused by a wide range of molecular and cellular pathologies. Current diagnosis of hearing loss depends of a combination of physiologic testing, patient history and in some cases genetic testing. Currently no biopsy or equivalent procedure exists to diagnose inner ear disorders. The goal of this study was to determine if miRNAs could be identified in human perilymph potentially leading to the development of biomarkers for inner ear disease. Analysis of miRNAs was carried out by evaluating miRNA targets in a cochlear transcriptome library (GSE128505) derived from human inner ear tissue harvested during surgery in which the inner ear is removed.
2019-03-19 | GSE128505 | GEO
Project description:A rat model of acute mitochondrial dysfunction in the cochlea is created by applying an irreversible mitochondrial complex II enzyme inhibitor, 3-NP, directly to the round window membrane. Treatment with 300 mM 3-NP results in temporary hearing loss (temporary threshold shift (TTS) model), whereas treatment with 500 mM 3-NP results in profound and permanent hearing loss (permanent threshold shift (PTS) model. Either treatment results with a primary histological change in the lateral wall spiral ligament. Because local ATP deprivation in the inner ear results from inhibition of inner ear mitochondrial function, this model replicates the etiology of inner ear energy failure caused by ATP deprivation due to inner ear ischemia. We used microarrays to detail the global programme of gene expression in the damaged cochlear lateral wall by 3NP and identified distinct classes of up-regulated/ down-regulated genes during the process. One and three day after administrated either 300 mM of 3-NP (TTS-1d and TTS-3d, respectably) or saline (Ctrl-1d and Ctrl-3d, respectably), rat cochear lateral wall in the apical side of the basal turn was harvested for RNA extraction and hybridization on Affymetrix microarrays.
2013-11-20 | E-GEOD-52500 | biostudies-arrayexpress
Project description:A rat model of acute mitochondrial dysfunction in the cochlea is created by applying an irreversible mitochondrial complex II enzyme inhibitor, 3-NP, directly to the round window membrane. Treatment with 300 mM 3-NP results in temporary hearing loss (temporary threshold shift (TTS) model), whereas treatment with 500 mM 3-NP results in profound and permanent hearing loss (permanent threshold shift (PTS) model. Either treatment results with a primary histological change in the lateral wall spiral ligament. Because local ATP deprivation in the inner ear results from inhibition of inner ear mitochondrial function, this model replicates the etiology of inner ear energy failure caused by ATP deprivation due to inner ear ischemia. We used microarrays to detail the global programme of gene expression in the damaged cochlear lateral wall by 3NP and identified distinct classes of up-regulated/ down-regulated genes during the process.
2013-11-20 | GSE52500 | GEO
Project description:The inner ear in mammals is derived from a simple ectodermal thickening called the otic placode. Through a series of complex morphological changes, the placode forms the mature inner ear comprising of the auditory organ (cochlea) and the vestibular/balance organs (utricle, saccule, and three semi-circular canals). The vast majority of genes known to be involved during inner ear development have been found through mutational screens or by chance. To identify genes that can serve as novel candidates required for inner ear development, and also candidate genes for uncloned human deafnesses, inner ear tissues from mouse embryos from E9 to E15 were microdissected and expression-profiled at half-day intervals. Also profiled was the non-inner ear mesenchymal tissue surrounding the inner ear tissue. Various patterns of gene expression were identified, and significant biological pathways that these genes represented were identified. Also identified were mouse genes whose human orthologs are located within uncloned non-syndromic deafness intervals, thus serving as candidates for sequence analysis. Keywords: Developmental timecourse
2007-08-14 | GSE7536 | GEO
Project description:In the study, we detailedly manifested the regulatory roles of histone modifications in neomycin-induced proliferation of Lgr5+ progenitor and HC regeneration by integrated RNA-seq and ChIP-seq analysis. we found 94 differentially expressed genes which are related to differential binding regions via analyzing ChIP-seq and RNA-seq data. we are delighted to find that H3K4me3 can modulate the expressions of 12 genes to involve in cell cycle, neural development, inner ear development, Wnt and Hippo signaling pathways to regulate proliferation and HC regeneration based on the protein interaction network and gene ontology (GO) functional annotation analysis.
2021-06-05 | GSE176158 | GEO
Project description:In order to characterize the various subpopulations of neurons present in the inner ear, we dissected out the cochleas from wild-type mice, removing non-neuronal populations as possible, then dissociated the tissue to obtain a single cell suspension and profiled these by single cell RNA-Seq.
2018-08-13 | GSE114759 | GEO
Project description:The inner ear in mammals is derived from a simple ectodermal thickening called the otic placode. Through a series of complex morphological changes, the placode forms the mature inner ear comprising of the auditory organ (cochlea) and the vestibular/balance organs (utricle, saccule, and three semi-circular canals). The vast majority of genes known to be involved during inner ear development have been found through mutational screens or by chance. To identify genes that can serve as novel candidates required for inner ear development, and also candidate genes for uncloned human deafnesses, inner ear tissues from mouse embryos from E9 to E15 were microdissected and expression-profiled at half-day intervals. Also profiled was the non-inner ear mesenchymal tissue surrounding the inner ear tissue. Various patterns of gene expression were identified, and significant biological pathways that these genes represented were identified. Also identified were mouse genes whose human orthologs are located within uncloned non-syndromic deafness intervals, thus serving as candidates for sequence analysis. Experiment Overall Design: Inner ear tissues from E9 to E15 were microdissected at half-day intervals. E9 is the earliest stage when the otic placode is clearly visible and able to be microdissected cleanly. E15 is the stage when all the organs of the inner ear have become established, as have the sensory hair and non-sensory support cells within those organs. For each of the stages from E9 to E10, whole inner ears were profiled. For each of the stages from E10.5 to E12, the primordial cochlear and vestibular organs were profiled separately. For each of the stages from E12.5 to E15, the cochlea and the saccule were profiled separately, whereas the utricle and the three ampullae were combined and profiled together. Any given tissue from any given stage was a collection of anywhere between 4 to 17 identical tissues, and was obtained in duplicate (i.e. from different litters). Hence, a total of 58 inner ear samples were obtained. Moreover, non-inner ear tissue found in the immediate vicinity of inner ear tissue was also obtained and profiled. Specifically, all non-inner ear tissue from E9 was profiled in duplicate. Non-inner ear tissue from E9.5 to E10.5 was pooled and profiled together (in duplicate), whereas that from E11 to E15 was pooled and profiled together (also in duplicate). Therefore, a total of 6 non-inner samples were obtained.
2008-06-15 | E-GEOD-7536 | biostudies-arrayexpress
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