Cochlea Neomycin Timecourse
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens Gallus gallus
PROVIDER: GSE6050 | GEO | 2007/02/01
SECONDARY ACCESSION(S): PRJNA97671
REPOSITORIES: GEO
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Project description:Much of human hearing loss is caused by loss of auditory hair cell (HC) function. Mammals cannot regenerate these essential mechanoelectrical transducers of sound. However, birds have retained the ability to regenerate HCs from surrounding supporting cells. To better understand hair cell regeneration, we have expression profiled the sensory epithelia from chicken cochleae and utricles. Pure sensory epithelia, consisting of HCs plus supporting cells, were damaged with either neomycin or laser treatment. Changes in gene expression at various points during regeneration were compared to undamaged control cultures on a custom microarray that interrogates the vast majority of transcription factor (TF) genes. These experiments involved multiple biological samples and hundreds of microarray comparisons. Keywords: timecourse
2007-02-01 | GSE5991 | GEO
Project description:Much of human hearing loss is caused by loss of auditory hair cell (HC) function. Mammals cannot regenerate these essential mechanoelectrical transducers of sound. However, birds have retained the ability to regenerate HCs from surrounding supporting cells. To better understand hair cell regeneration, we have expression profiled the sensory epithelia from chicken cochleae and utricles. Pure sensory epithelia, consisting of HCs plus supporting cells, were damaged with either neomycin or laser treatment. Changes in gene expression at various points during regeneration were compared to undamaged control cultures on a custom microarray that interrogates the vast majority of transcription factor (TF) genes. These experiments involved multiple biological samples and hundreds of microarray comparisons. Keywords: timecourse
2007-02-01 | GSE6051 | GEO
Project description:Much of human hearing loss is caused by loss of auditory hair cell (HC) function. Mammals cannot regenerate these essential mechanoelectrical transducers of sound. However, birds have retained the ability to regenerate HCs from surrounding supporting cells. To better understand hair cell regeneration, we have expression profiled the sensory epithelia from chicken cochleae and utricles. Pure sensory epithelia, consisting of HCs plus supporting cells, were damaged with either neomycin or laser treatment. Changes in gene expression at various points during regeneration were compared to undamaged control cultures on a custom microarray that interrogates the vast majority of transcription factor (TF) genes. These experiments involved multiple biological samples and hundreds of microarray comparisons. Keywords: timecourse
2007-02-01 | GSE6052 | GEO
Project description:Sensorineural hearing loss is included in the most common disabilities, and often caused by loss of sensory hair cells in the cochlea. Hair cell regeneration has long been a main target for developing novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration occurs in very limited situations, while auditory epithelia of non-mammalians retain the capacity for hair cell regeneration. In the avian basilar papilla, an auditory sensory epithelium, supporting cells, which are sources for regenerated hair cells, are usually quiescent, while hair cell loss induces both direct transdifferentiation of supporting cells and mitotic division of supporting cells. In the present study, we aimed to establish an explant culture model for hair cell regeneration in chick basilar papillae, and validated usefulness of our model to investigate the initial phase of hair cell regeneration. Histological assessments demonstrated that hair cell regeneration via direct transdifferentiation of supporting cells occurred in our model. Labeling assay using 5-ethynyl-2'-deoxyuridine (EdU) revealed the occurrence of mitotic division of supporting cells in the specific location in basilar papillae, while no EdU labeling was identified in newly generated HCs. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, which is consistent with previous findings. In addition, unbiased analyses of RNA sequencing data indicated novel genes and signaling pathways that could be related to the ignition of supporting cell activation in chick basilar papillae. These results indicate the advantages of our model using explant cultures of chick basilar papillae for exploring molecular mechanisms for hair cell regeneration. Further studies such as single-cell RNA sequencing will allow us to capture the spatiotemporal information by using our explant culture model.
2020-10-23 | GSE154375 | GEO
Project description:The inner ear utilizes sensory hair cells as mechano-electric transducers for sensing sound and balance. In mammals, these sensory hair cells lack the capacity for regeneration and if damaged lead to hearing or balance disorders. However, non-mammalian vertebrates such as birds maintain their regenerative abilities throughout their life. In a previous study we conducted a gene expression profiling time course of regenerating sensory epithelia (SE) in avian cochlea and utricle on a custom transcription factor microarray following damage by both laser and chemical ablation. We identified several known signaling cascades such as The Pax-Eya-Six-Dach pathway, Ap-1 pathway, the Tgf-β pathway and sonic hedgehog signaling that are differentially expressed during SE regeneration. In this study we selected 27 of these genes for knockdown by siRNA or small molecule inhibition to determine their requirement for SE regeneration and identify downstream targets. We assessed phenotypes using a 96 well proliferation assay and expression profiled each knockdown on a custom transcription factor microarray. Using these techniques we have determined several genes that are required for SE proliferation and identified novel epistatic relationships between many of these genes. Pure sensory epithelia was isolated from avian utricles. Sensory epithelia was physically dissociated and grown in 96 well cultures for 3 days. Prior to confluency, dissociated sensory epithelia were transfected with siRNAs (12 pmol/well) or small molecule inhibitor in 0.1% DMSO. RNA was isolated 24 hrs post transfection and assayed on a custom oligonucleotide transcription factor microarray compared to controls (GFP siRNA or 0.1% DMSO only). siRNA: CEBPG, JunD, BTAF1, LRP5, PAX2, PAX5, PAX7, Wnt4, BCL11A, CBX3, CBX4, CTNNB1, CUTL1, MYT1L, RARA, TIMELESS, TRIP15, PAX3, EZH2, HES1, ID1, CDKN1B, and PPARGC1 small molecule inhibition: IGF, MAPK, SHH, and JNK
2010-07-02 | E-GEOD-16842 | biostudies-arrayexpress
Project description:The inner ear utilizes sensory hair cells as mechano-electric transducers for sensing sound and balance. In mammals, these hair cells lack the capacity for regeneration. Unlike mammals, hair cells from non-mammalian vertebrates, such as birds, can be regenerated throughout the life of the organism making them a useful model for studying inner ear genetics pathways. The zinc finger transcription factor GATA3 is required for inner ear development and mutations cause sensory neural deafness in humans. In the avian cochlea GATA3 is expressed throughout the sensory epithelia; however, expression is limited to the striola of the utricle. The striola corresponds to an abrupt change in morphologically distinct hair cell types and a 180° shift in hair cell orientation. We used 3 complimentary approaches to identify potential downstream targets of GATA3 in the avian utricle. Specifically we used microarray expression profiling of GATA3 knockdown by siRNA and GATA3 over-expression treatments as well as direct comparisons of GATA3 expressing cells from the striola and non GATA3 expressing cells from the extra-striola. Whole utricle specimens were treated with streptomycin for 24 hrs, rinsed and allowed to recover for an additional 24 hrs. Whole utricles were transfected with either GATA3 or GFP 21mer synthetic siRNAs for an additional 48 hrs and pure sensory epithelia were isolated. There are 2 biological samples and experiments include technical replicates as well as dye-switches for a total of 8 microarrays.
2010-06-24 | E-GEOD-14785 | biostudies-arrayexpress
Project description:To understand the basic biological property of hair cells (HCs) from lower vertebrates, we examined transcriptomes of adult zebrafish HCs. GFP-labeled HCs were isolated from the utricle, saccule, and lagena, the three inner-ear sensory epithelia of a pou4f3 promoter-driven GAP-GFP line of transgenic zebrafish. 2,000 HCs and 2,000 non-sensory cells from the inner ear were individually collected by suction pipet technique. RNA sequencing was performed and the resulting sequences were mapped, analyzed, and compared. Comparisons allow us to identify enriched genes in HCs, which may underlie HC specialization.
2018-02-06 | GSE92559 | GEO
Project description:In contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor beta receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae.
2023-01-10 | GSE209791 | GEO
Project description:Mammalian cochlea hair cells can be regenerated from the adjacent supporting cells in many ways, however, the newly hair cells are immature and without hearing function almost. The expression of Atoh1 is an important maker of the appearance of newly hair cells, many approaches of inner ear hair cells’ regeneration are concerned with the transcription factor Atoh1. However, most new HCs are immature HCs, and they do not have the function of mature HCs and eventually die a few weeks after regeneration. Thus promoting the maturation and survival of new HCs is the primary focus of HC regeneration field. We used RNA-Seq analysis to compare the differences between the transcriptomes of Atoh1 overexpression-induced new HCs and the original HCs, and to define the factors that might help to promote the maturation and survival of new HCs.
2019-04-10 | GSE129533 | GEO
Project description:Murine auditory and vestibular epithelia were separated into hair-cells (HCs), epithelial non-sensory cells (ENSCs) and non-epithelial cells (NECs) by flow cytometry. Gene expression levels were recorded in independent triplicates from the sorted cells using Illumina whole genome expression microarrays
2015-10-12 | GSE64543 | GEO