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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:Meis genes have been shown to control essential processes during development of the central and peripheral nervous system. Here we have defined the roles of the Meis2 gene during vertebrate inner ear induction and the formation of the cochlea. Meis2 is expressed in several tissues required for inner ear induction and in non-sensory tissue of the cochlear duct. Global inactivation of Meis2 in the mouse leads to a severely reduced size of the otic vesicle. Tissue-specific knock outs of Meis2 reveal that its expression in the hindbrain is essential for inner ear induction. Inactivation of Meis2 in the inner ear itself leads to an aberrant coiling of the cochlear duct. By analyzing transcriptomes obtained from Meis2 mutants and ChIPseq analysis of an otic cell line we define candidate target genes for Meis2 which may be directly or indirectly involved in cochlear morphogenesis. Taken together, these data show that Meis2 is essential for inner ear formation and provide an entry point to unveil the network underlying proper coiling of the cochlear duct.
2021-03-12 | GSE166072 | GEO
Project description:A balance of morphogen gradients during embryogenesis is thought to determine the identity of inner ear end organs. We applied this developmental principle to aggregates of human pluripotent stem cells and found that modulations of Sonic Hedgehog and WNT signaling promote stem cell-derived otic progenitors to express ventral otic markers. Strikingly, these ventralized otic progenitors gave rise to hair cells with short hair bundles comprised of stereocilia arrayed in a geometry reminiscent of cochlear hair cells. Moreover, these ventralized hair cells expressed multiple markers defining outer or inner hair cells in the cochlea. These results reveal that early morphogenic signals are sufficient for not only establishing cochlear gene expression, but also defining structural properties pertaining to the cochlear sensory epithelium.
2022-04-14 | GSE200629 | 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:In this study, we generated a human inner ear atlas containing three stages of inner ear development. This atlas was used to evaluate the differentiation approach of human pluripotent stem cells in to complex inner ear tissue, known as inner ear organoids. The primary goal of this single-nucleus RNA-sequencing analysis was to capture the cell type diversity of the human inner ear at different stages of development. The secondary goal was to define the similarity of organoid-derived inner ear cell types with the atlas-derived human inner ear cell types and to determine the developmental stage of the organoid-derived inner ear cell types.
2023-06-05 | GSE213796 | GEO
Project description:Retinoblastoma gene (Rb1) is required for proper cell cycle exit in the developing mouse inner ear and its deletion in the embryo leads to proliferation of sensory progenitor cells that differentiate into hair cells and supporting cells. In the Pou4f3-Cre:Rb1 flox/flox (Rb1 cKO) inner ear, utricular hair cells differentiate and survive into adulthood whereas differentiation and survival of cochlear hair cells are impaired. To comprehensively survey the pRb pathway in the mammalian inner ear, we performed microarray analysis of Rb1 cKO cochlea and utricle. P6 or 2-month control and Rb1 cKO littermates were euthanized and the inner ear tissues were dissected. Total RNA was extracted from the pooled samples. Technical duplicates of the pooled RNA were used for microarray.
2011-05-31 | E-GEOD-25732 | biostudies-arrayexpress
Project description:Otic ectoderm gives rise to almost all cell types of the inner ear; however, the mechanisms that link transcription factors, chromatin, lineage commitment and differentiation capacity are largely unknown. Here we show that Brg1 chromatin-remodeling factor is required for specifying neurosensory lineage in the otocyst and for inducing hair and supporting cell fates in the cochlear sensory epithelium. Brg1 interacts with the critical neurosensory-specific transcription factors Eya1/Six1, both of which simultaneously interact with BAF60a or BAF60c. Chromatin immunoprecipitation-sequencing (ChIP-seq) and ChIP assays demonstrate Brg1 association with discrete regulatory elements at the Eya1 and Six1 loci. Brg1-deficiency leads to markedly decreased Brg1 binding at these elements and loss of Eya1 and Six1 expression. Furthermore, ChIP-seq reveals Brg1-bound promoter-proximal and distal regions near genes essential for inner ear morphogenesis and cochlear sensory epithelium development. These findings uncover essential functions for chromatin-remodeling in the activation of neurosensory fates during inner ear development.
2020-04-17 | GSE119545 | GEO
Project description:Retinoblastoma gene (Rb1) is required for proper cell cycle exit in the developing mouse inner ear and its deletion in the embryo leads to proliferation of sensory progenitor cells that differentiate into hair cells and supporting cells. In the Pou4f3-Cre:Rb1 flox/flox (Rb1 cKO) inner ear, utricular hair cells differentiate and survive into adulthood whereas differentiation and survival of cochlear hair cells are impaired. To comprehensively survey the pRb pathway in the mammalian inner ear, we performed microarray analysis of Rb1 cKO cochlea and utricle.
2011-06-01 | GSE25732 | GEO
Project description:In order to elucidate molecular mechanisms of noise-induced hearing loss in the cochlea (inner ear), transcriptome of the cochlear sample was analyzed after induction of hearing loss by exposure to intense noise in mice. Cochlear transcriptome was analyzed at 3 hours following the noise exposure.
2020-01-14 | GSE137817 | GEO
Project description:The molecular characterization of early stages of human inner ear development is limited by the difficulty in accessing samples at early gestational stages. Some aspects of inner ear morphogenesis can be recapitulated using pluripotent stem cell directed differentiation in inner ear organoids (IEOs). Once validated and benchmarked, these models could provide a unique tool to complement and refine our understanding of human otic differentiation and could be used to model developmental defects.Here we provide a first characterization of early human embryonic otocyst development and compare the primary tissue to the iPSC-derived inner ear cell types. Multiplex immunostaining and single cell RNA sequencing were used to characterize human iPSC-derived IEOs at 3 key developmental steps, providing a new and unique signature of in vitro derived otic- placode, epithelium, neuroblasts and sensory epithelia. The expression and localization of key markers were further evaluated in human embryos. We show that the otic placode derived in vitro (day 8-12) matches marker expression of Carnegie Stage (CS) 11 embryos, and subsequently (day 20-40) gives rise to otic epithelia and neuroblasts comparable to the CS13 embryonic stage. Differentiation of sensory epithelia, including supporting cells and hair cells, starts in vitro at day 50-60 of culture. The maturity of these cells is equivalent to vestibular sensory epithelia at week 10 or cochlear tissue at week 12 of development, prior to functional onset. Taken together these data indicates that the current state of the art protocol enables the specification of bona fide otic tissue, supporting further application of IEOs to model inner ear biology and disease
2023-08-22 | GSE229148 | GEO