Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and Pou4f3(Δ/+) Cochlear Transcriptomes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139145 | GEO | 2019/10/22
REPOSITORIES: GEO
Similar Datasets
Project description:Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and Pou4f3(Δ/+) Cochlear Transcriptomes
| PRJNA578633 | ENA
Project description:Hearing loss is often due to the absence or the degeneration of hair cells in the cochlea. Understanding the mechanisms regulating the generation of hair cells may therefore lead to better treatments for hearing disorders. To elucidate the transcriptional control mechanisms specifying the progenitor cells (i.e. prosensory cells) that generate the hair cells and support cells critical for hearing function, we compared chromatin accessibility using ATAC-seq in sorted prosensory cells (Sox2-EGFP+) and surrounding cells (Sox2-EGFP-) from E12, E14.5 and E16 cochlear ducts. In Sox2-EGFP+, we find greater accessibility in and near genes restricted in expression to the prosensory region of the cochlear duct including Sox2, Isl1, Eya1 and Pou4f3. Furthermore, we find significant enrichment for the consensus binding sites of Sox2, Six1 and Gata3—transcription factors required for prosensory development—in the open chromatin regions. Over 2,200 regions displayed differential accessibility with developmental time in Sox2-EGFP+ cells, with most changes in the E12-14.5 window. Open chromatin regions detected in Sox2-EGFP+ cells map to over 48,000 orthologous regions in the human genome that include regions in genes linked to deafness. Our results reveal a dynamic landscape of open chromatin in prosensory cells with potential implications for cochlear development and disease.
2019-06-21 | GSE131775 | 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: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:This study investigates how lead exposure triggers cochlear synaptopathy and hearing loss in mice. Young-adult CBA/J mice were given lead acetate in drinking water for 28 days. We assessed hearing thresholds, outer hair cell activity, and synaptic changes in the cochlea. Lead exposure raises hearing thresholds, indicating cochlear synaptopathy. Notably affects synapses in the basal turn without impacting outer hair cells. In addition to this, lead altered the abundance of 352 synaptic proteins, with the synaptic vesicle cycle pathway prominently affected. Lead-induced cochlear synaptopathy targets basal cochlear regions, implicating synaptic vesicle cycle signaling in hearing loss. Revealing specific mechanisms behind lead-induced hearing deficits enhances targeted interventions and preventive strategies, advancing our understanding of lead induced hearing loss.
2024-10-17 | PXD050415 | Pride
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:Juvenile and mature mouse cochleae contain various low-abundant, vulnerable sensory epithelial cells embedded in the calcified temporal bone, making it challenging to profile the dynamic transcriptome changes of these cells during maturation at the single-cell level. Here we performed the 10X Genomics single-cell RNA sequencing (scRNA-seq) of mouse cochleae at postnatal days 14 (P14) and 28. We attained the transcriptomes of multiple cell types, including hair cells, supporting cells, spiral ganglia, stria fibrocytes, and immune cells. Our hair cell datasets are consistent with published transcripts from bulk RNA seq and scRNA-seq. We also mapped known deafness genes to corresponding cochlear cell types. Importantly, pseudotime trajectory analysis revealed that inner hair cells peak their maturation at P14 while outer hair cells continue to develop until P28. We further identified and confirmed a long noncoding RNA gene Miat expressed during maturation in cochlear hair cells and spiral ganglia neurons. Our transcriptomes of juvenile and mature mouse cochlear cells provided the sequel to those previously published at late embryonic and early postnatal ages and will be valuable resources to investigate cochlear maturation at single-cell resolution.
2022-08-19 | GSE202920 | GEO
Project description:Previous unbiased screening for the nucleosome binding affinity of transcription factors predicts that POU domain transcription factors have strong nucleosome binding potential. Here using reprogramming strategy we found that POU4F3 has pioneer factor activity at ATOH1 target elements that require POU4F3 for their accessibility.
2021-07-09 | GSE150279 | GEO
Project description:The cochlear nucleus is the first central pathway involved in the processing of peripheral auditory activity. It is heterogeneous in neuronal populations and physiologic responses and is organized in three major subdivisions: the anterior ventral cochlear nucleus (AVCN), the posterior ventral cochlear nucleus (PVCN) and the dorsal cochlear nucleus (DCN). Although each region demonstrates multiple cell types and functions, there are predominant populations of neurons in each region that underlie the principal role each subdivision plays in auditory processing. Little is known of the underlying genetic contribution to these properties. This study sought to identify genes expressed in the subdivisions of the cochlear nucleus that may account for the anatomical and physiological characteristics of each subdivision. These data provide a genetic basis for understanding normal auditory processing in the cochlear nucleus and a template for investigating changes that may occur with hearing loss, the generation and percept of tinnitus, and central processing disorders. Keywords: normal, comparative Brown Norway rats (n=40, female, 45days) were anesthetized and decapitated. Brains were rapidly removed and the subdivisions of the cochlear nucleus (AVCN, PVCN and DCN) dissected on dry ice. Total RNA was extracted and tested for concentration and purity by spectrophotometry and integrity by gel electrophoresis. SAGE was performed using the NlaIII enzyme and Invitrogen SAGE kit. Concatemers were commercially sequenced and imported into eSAGE (Margulies and Innis, 2000) for tag extraction and frequency.
2005-12-31 | E-GEOD-3628 | biostudies-arrayexpress
Project description:Mutations in the gene for Norrie disease protein (Ndp) cause syndromic deafness and blindness. We show that cochlear function in an Ndp knockout (KO) mouse deteriorated with age: at P3-P4, hair cells (HCs) showed progressive loss of Pou4f3 and Gfi1, key transcription factors for HC maturation, and Myo7a, a specialized myosin required for normal function of HC stereocilia. Loss of expression of these genes correlated to increasing HC loss and profound hearing loss by 2 months of age. We show that overexpression of the Ndp gene in neonatal supporting cells or, remarkably, upregulation of canonical Wnt signaling in HCs rescued HCs and cochlear function. We conclude that Ndp secreted from supporting cells orchestrates a transcription factor network for the maintenance and survival of HCs and that increasing the level of b-catenin, the intracellular effector of Wnt signaling, is sufficient to replace the functional requirement for Ndp in the cochlea.
2021-09-04 | GSE173393 | GEO