Version: 8.0.0Date: Tue Jan 28 2025
Category
Expression data of miRNA from mice cochlea during aging
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-45026, GEO:GSE45026
Tags: strain study, baseline, age
Summary: To identify which miRNAs are involved in the onset and progression of age-related hearing loss in the mammalian cochlea We used miRNA microarrays to screen the miRNAs which exhibit the drastic changes in their expressing level during the aging of the cochlea The organ of Corti (OC), the major pathological sites of presbycusis in cochlea, was collected separately at 3 timepoints during the life span. Two strains were selected: C57bl/6j (as accelerated prebycusis model) and CBA/J (as naturally occured presbycusis model). The selected timepoints were: Postnatal 21 days (P21), 3 month (3m) and 9 month (9m) for C57 mice, and P21, 9m, 16m for CBA mice.
Symbol: Expression data of miRNA from mice cochlea during aging
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE83356
Tags: baseline, cell type, developmental stage
Summary: This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 1 and postnatal day 6. mRNA profiles of supporting cells (GFP+) and all other cochlear cell types (GFP-), two replicates each, at P1 and P6 mice were generated by deep sequencing using Illumna TruSeq.
Symbol: RNA-seq analysis of neonatal mouse cochlear supporting cells [NonTreated_JM]
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE135703
Tags: baseline, age
Summary: Characterizing adult cochlear supporting cell transcriptional diversity using scRNA-Seq Hearing loss is a significant disability that impacts 432 million people worldwide. A significant proportion of these individuals are dissatisfied with or do not have access to available treatment options which include hearing aids and cochlear implants. An alternative approach to restore hearing would be to regenerate lost cells, including hair cells in the adult cochlea. Such therapy would require restoration of the organ of Corti's complex architecture, necessitating regeneration of both mature hair cells and supporting cells. We characterize the first single-cell adult cochlear supporting cell transcriptomes with the goals of: (1) demonstrating their transcriptional distinctiveness from perinatal cochlear supporting cells, (2) providing a metric for future attempts at regenerating mature cochlear supporting cells by identifying both cell type-specific and regional-specific expression, and (3) identify cell cycle gene expression present in adult supporting cells at the single cell level which may establish a basis for targeting cell cycle regulation pathways to force these cells out of quiescence. FACS-purified P60 and P120 Lfng-EGFP cochlear supporting cells scRNA-Seq on Fluidigm C1 platform Grant information: ZIA DC000088-05
Symbol: Characterizing adult cochlear supporting cell transcriptional diversity using single-cell RNA-Seq: Validation...in the adult mouse and translational implications for the adult human cochlea
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-4866, GEO:GSE4866
Tags: WT vs. mutant, genotype
Summary: Mitochondrial DNA (mtDNA) mutations may contribute to aging and age-related disorders. Previously, we created mice expressing a proofreading-deficient version of the mtDNA polymerase gamma (Polg) which accumulate age-related mtDNA mutations and display premature aging. Here we performed microarray gene expression profiling to identify mtDNA mutation-responsive genes in the cochlea of aged mitochondrial mutator mice. Age-related accumulation of mtDNA mutations was associated with transcriptional alternations consistent with reduced inner ear function, mitochondrial dysfunction, neurodegeneration, and reduced cell structural modulation. Hearing assessment and histopathological results confirmed that aged PolgD257A/D257A (D257A) mice exhibited moderate hearing loss and severe cochlear degenerations. Age-related accumulation of mtDNA mutations also resulted in alternations in gene expression consistent with induction of apoptosis, proteolysis, stress response, and reduced DNA repair. TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay confirmed that the cochleae from aged D257A mice showed significantly more TUNEL positive cells compared to wild-type (WT) mice. The levels of cleaved caspase-3 were also found to increase in the cochleae of aged D257A mice. These observations provide evidence that age-related accumulation of mtDNA mutations is associated with apoptotic cell death in aged cochlea. Our results provide the first global view of molecular events associated with mtDNA mutations in postmitotic tissue, and suggest that apoptosis is the major mechanism of mtDNA mediated cell death in the development of age-related hearing disorder. Experiment Overall Design: To determine the effects of age-related accumulation of mtDNA mutations, each WT sample (n = 5) was compared to each D257A sample (n = 5), generating a total of twenty-five pairwise comparisons. Genes with significantly altered expression levels were sorted into gene ontology biological process categories. Experiment Overall Design: Gene expression change was called statistically significant when at least one gene was called present in a group, the P value was < 0.0500, FC was > 1.1, and FDR was > 30.00 for identification of mtDNA mutations-induced genes. Experiment Overall Design: Affymetrix standard spike controls were used in all experiments (eukaryotic hybridization control kit). Quality control measures were not used. No replicates were done. Dye swap was not used.
Symbol: Transcription profiling by array of cochlea from PolgD257A/D257A mice
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-11821, GEO:GSE11821
Tags: WT vs. mutant, genotype
Summary: Different mutations in the gene encoding humans IGF-I cause intrauterine growth retardation, postnatal growth failure, microcephaly, mental retardation, bilateral sensorineural deafness and multiple dysmorphic features. Insight into the role of IGFs in inner ear cochlear ganglion neurogenesis has come from the study of genetically modified mice. Postnatal cochlear development is severely impaired in mice Igf1-/-, which develop smaller cochlea and cochlear ganglia, an immature tectorial membrane and they display a significant decrease in the number and size of auditory neurons. We used microarrays to define the genetic signatures of Igf-1 +/+ and Igf-1-/- mouse cochea and identify the differentially expressed genes. Experiment Overall Design: Cochleae from two E18.5 were isolated from both Igf-1+/+ wild type and Igf-1-/- null mice and pooled to obtain RNA. Heterozygous male and female with a genetic background C57BL/6J were mated to obtain embryos 18.5 days post coitus (E18.5). Three independent pools were used. Cochlear tissues included the otic capsule but not vestibular tissues.
Symbol: Transcription profiling of mouse Igf-1 -/- and Igf-1+/+ cochleas
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE137299
Tags: baseline, developmental stage
Summary: The organ of Corti, located in the floor of the scala media of the cochlea, acts as the primary sensory transducer of sound in mammals. This remarkable structure comprises a highly diverse cellular mosaic that includes two unique types of mechanosensory hair cells and an undefined number of associated supporting cell types. All of these cells are believed to arise from a developmental equivalence group referred to as the prosensory domain that is similarly thought to arise from a proneurosensory population that develops in the anterior-ventral region of the otocyst. The results of both classical embryologic manipulations and modern molecular genetic experiments suggest that otocyst precursor cells proceed through several rounds of lineage restriction that progressively specify subsets of cells as prosensory cells and ultimately as either hair cells or supporting cells. However, the relatively small sizes of the otocyst and inner ear have hindered efforts to determine the full diversity of cell types within the mature cochlea and to identify the transitional cell types that exist during development. The recent development of droplet-based methods for isolation and subsequent transcriptional profiling of individual cells provides a potential method to address both of these challenges. Therefore, we dissected, dissociated and then captured over 27,000 epithelial cells from the developing cochlear duct at specific time points between E14 and P7. We characterized the transcriptomic profiles of cochlear epithelium celltypes of E14, E16, P1, P7 wild type (WT) mice at a single cell resolution using 10x Chromium and Illumina sequencing platforms. Data contain over 27,000 single cells.
Symbol: Characterization of cochlear development at the single cell level
RNA-seq analysis of neonatal mouse cochlear hair cells
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE65633
Tags: anatomical structure, baseline, cell type
Summary: This study examined transcripts that are enriched in neonatal mouse cochlear hair cells. Hair cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which the endogenous Atoh1 gene was fused with GFP Two replicates of GFP+ hair cells were compared with all other cochlear cell types that were GFP-
Symbol: RNA-seq analysis of neonatal mouse cochlear hair cells
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-15496, GEO:GSE15496
Tags: anatomical structure, baseline
Summary: MicroRNAs (miRNAs) inhibit the translation of target mRNAs and affect, directly or indirectly, the expression of a large portion of the protein-coding genes. This study focuses on miRNAs that are expressed in the mouse cochlea and vestibule, the two inner ear compartments. To identify miRNAs that are expressed in the vertebrate developing inner ear, we used miRNA microarrays. Similar miRNA profiles were found in newborn (P0) mouse whole cochleae and vestibules. 105 miRNAs were found to be expressed in the whole P0 cochlea and 114 miRNAs expressed in the whole P0 vestibule with average intensities higher than twice the global background, out of 206 included in the arrays. Only 24 miRNAs were found to have different levels of expression in these whole organs, and these differences were mild (15-40%). The microarray results were intersected with two bioinformatic complementary approaches in order to choose candidate miRNAs that are predicted to be expressed specifically in the inner ear sensory epithelia (see the paper). Six small (<40 nt) RNA samples were hybridized with 4 microarrays (to save costs, some of the microarrays were hybridized with two different samples, labeled with different CyDyes â Cy3 and Cy5). Each RNA sample contains small RNAs (<40 nt) pooled from at least 20 newborn cochleae or vestibules, and there are 3 different samples for each organ. However, one of the samples (WT_P0_whole_Cochlea_3_V4) was hybridized with a different array than the other samples (printed from the same probes, but at a different date), and therefore excluded from the analysis described in the paper. Each microarray contains at least 4 identical spots per each probe that may be considered as technical replicates. Four of the samples were hybridized in parallel at the same day to two microarrays, and the dyes were swaped: First microarray: WT_P0_whole_Cochlea_1 (Cy3) [GSM388075] and WT_P0_whole_Vestibule_2 (Cy5) [GSM388635]; second microarray: WT_P0_whole_Cochlea_2 (Cy5) [GSM388633] and WT_P0_whole_Vestibule_1 (Cy3) [GSM388634]. The other 2 samples: WT_P0_whole_Vestibule_3 (Cy3) [GSM388637] and WT_P0_whole_Cochlea_3_V4 (Cy3) [GSM388660] were hybridized to two individual microarrays, at different dates. The miRNA profile in the cochlear and vestibular samples were compared: the vestibular samples are considered as the âexperimentâ samples, and the cochlear samples â as âreferenceâ. Positive control probes (labeled as âcontrol 1â in raw data) were added to RNA samples before labeling. The average of empty and buffer spots was used to calculate the global background of each array, and only miRNAs with an average expression higher than twice the fold of the array global background at least in one of the tissues were considered as expressed.
Symbol: MicroRNA expression in the newborn mouse cochlea and vestibule
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE137721
Tags: WT vs. mutant, genotype
Summary: Noncoding microdeletion in mouse Hgf disrupts neural crest migration into the stria vascularis, reduces the endocochlear potential and suggests the neuropathology for human nonsyndromic deafness DFNB39 Cochleae from 3 mice homozygous for a 10bp deletion in intron 5 of the Hgf gene and 3 wild-type littermates. Total RNA extracted, converted to cDNA, fragmented to make Illumina libraries and sequenced (93x93 PE) on an Illumina HiSeq1500. Reads were mapped to the mouse genome (GRCm38.vM11) with STAR, and differential gene expression analyzed with DeSeq2.
Symbol: RNA-seq analyses of cochleae from a mouse model of DFNB39
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-70659, GEO:GSE70659
Tags: WT vs. mutant, genotype
Summary: CMP-Neu5Ac hydroxylase (Cmah) disruption caused several abnormalities and diseases including hearing loss in old age. However, underling molecular mechanisms that give rise to age-related hearing loss (AHL) in Cmah-null mouse are still obscure. To identify differential gene expression profiles associated with Cmah disruption, we performed microarray analysis using Illumina MouseRef-8 v2 Expression BeadChip, using the cochlear tissues from a control mouse and a Cmah-null mouse. Total RNA was extracted and purified from the cochlear tissues of WT and Cmah-null mice using RNeasy columns (Qiagen; Valencia, CA, USA) according to the manufacturer's protocol. The RNA quality was verified using an Agilent Bioanalyzer 2100 (Agilent Technologies; Palo Alto, CA, USA) using the RNA 6000 Pico Assay. Generation of double-stranded cDNA, preparation and labeling of cRNA, hybridization to Mouse Ref-8 v2.0 Expression BeadChip (Illumina, Inc.; San Diego, CA, USA), washing, and scanning were all performed according to the standard Illumina protocol. Arrays were scanned using the Illumina Bead Array Reader Confocal Scanner.
Symbol: Gene expression profile in the cochlear tissue of Cmah-null mouse
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-56866, GEO:GSE56866
Tags: baseline, cell type
Summary: The transcriptome is the complete set of all RNA transcripts produced by the genome in a cell and reflects the genes that are being actively expressed. Transcriptome analysis is essential for understanding the genetic mechanism controlling the phenotype of a cell. Using DNA microarray technique we examined transcriptomes of 2,000 individually collected inner (IHCs) and outer hair cells (OHCs), two types of auditory sensory cells critical for hearing. Among approximately 16,645 and 17,711 transcripts considered to be expressed, 1,296 and 256 genes showed significant differential expression in IHCs and OHCs, respectively. The top ten differentially expressed genes include Slc17a8, Dnajc5b, Slc1a3, Atp2a3, Osbpl6, Slc7a14, Bcl2, Bin1, Prkd1, Map4k4 in IHCs, and Slc26a5, C1ql1, Strc, Dnm3, Plbd1, Lbh, Olfm1, Plce1, Tectb, Ankrd22 in OHCs. Many unknown sequences and non-coding RNAs were also expressed in hair cells. The differentially expressed genes underlie the genetic mechanism for unique functions of IHCs and OHCs. The total RNA was extracted from the collected pools of single outer hair cell (OHC) and inner hair cell (IHC). Their whole-genome transcriptome expression was detected using GeneChip microarray analysis. The analysis and comparison between OHC and IHC allow us to determine what genes are expressed and what genes are uniquely or differential expressed in each population.
Symbol: Transcriptomes of the Cochlear Inner and Outer Hair Cells
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-13421, GEO:GSE13421
Tags: baseline
Summary: This data set is intended as a public resource documenting the identity of roughly 10,000 genes that are abundantly expressed in the mouse cochlea. The data have many uses, including for making comparisons with proteomics studies, and for comparisons of expression profiles with other mouse strains and with other species. The CBA/CaJ strain was chosen because of its lack of known vulnerabilities to premature cochlear degeneration or to extreme reactions to cochlear stresses. It may therefore be considered a "normal" mouse. No experimental manipulations were done on the mice of this study. Contamination of the results by genes expressed in the surrounding petrous bone and from those in blood cells was minimized. Experiment Overall Design: 8 replicates, pooled ears from each of 8 mice
Symbol: Transcription profiling of mouse CBA/CaJ cochlea gene expression profile
scRNA-seq of P2 and P7 mouse cochlea and utricle
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE172327
Tags: anatomical structure, baseline, developmental stage
Summary: Cell types in the cochlea and utricle were identified using scRNA-seq of each tissue. Examination of expression patterns of genes expressed in day 2 and day 7 mouse cochlea and utricle
Symbol: scRNA-seq of P2 and P7 mouse cochlea and utricle
Profiling mouse cochlear cell maturation using 10X Genomics single-cell transcriptomics
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE202920
Tags: baseline, age
Summary: 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.
Symbol: Profiling mouse cochlear cell maturation using 10X Genomics single-cell transcriptomics
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-6045, GEO:GSE6045
Tags: baseline, age
Summary: Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. The DBA/2J (DBA) mice have been used as a model of AHL and undergoes progressive, age-related hearing loss by 12 weeks of age. Here we analyzed cochlear gene expression of 7-week-old and 36-week-old DBA mice using microarrays. Auditory brainstem response (ABR) analysis confirmed that severe age-related hearing loss occurred in 36-week-old mice, whereas moderate hearing loss occurred in 7-week-old mice. Comprehensive gene expression analysis identified genes correlated with AHL and revealed that 15 mitochondrial process categories, including "mitochondrial electron transport chain," "oxidative phosphorylation," "respiratory chain complex I," "respiratory chain complex IV," and "respiratory chain complex V," were statistically associated with AHL-correlated genes in the cochlea of 36-week-old DBA mice, and that 25 genes encoding components of the mitochondrial respiratory chain (respiratory chain complex I, IV, and V) were significantly down-regulated in the cochlea. These observations provide evidence that AHL is associated with down-regulation of genes involved in the mitochondrial respiratory chain in the cochlea of DBA mice, and suggest that mitochondrial respiratory chain dysfunction may be a key feature of AHL in mammalian cochlea. Experiment Overall Design: To determine the effects of age-related hearing loss, each 7-week-old sample (n = 3) was compared to each 36-week-old sample (n = 3), generating a total of nine pairwise comparisons. Using DAVIS and EASE, the identified genes were assign to "GO: Biological Process" categories of Gene Ontology Consortium. Furthermore, we used EASE to determine the total number of genes that were assigned to each biological process category, and to perform Fisher exact test. Quality control measures were not used. No replicates were done. Dye swap was not used.
Symbol: Transcription profiling of mouse age-related hearing loss cochlea in DBA/2J
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-57782, GEO:GSE57782
Tags: strain study, baseline, age
Summary: Age-related hearing loss is a progressive sensorineural hearing loss that occurs as people get older. Degeneration of the organ of Corti and atrophy of the lateral wall of the cochlear duct (or scala media) in the inner ear are the two primary causes. MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA/protein targets, are important regulators of cellular senescence and aging. We examined the change of miRNA gene expression profiles in the lateral wall of the cochlear duct in two mouse strains during aging The total RNA was extracted from the lateral wall of cochlear duct from CBA/J and C57BL/6J mice at different ages. The expression profile of miRNAs was examined by miR microarray GeneChip.
Symbol: MicroRNAs Involved in Aging of the Lateral Wall of the Cochlear Duct
Gene expression data from rat cochlear lateral wall after 3NP damage
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE52500
Tags: unclassified
Summary: 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.
Symbol: Gene expression data from rat cochlear lateral wall after 3NP damage
Gene expression analysis of the cochlea of Opa1 KO mice
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE232051
Tags: WT vs. mutant, genotype
Summary: RNA was extracted from dissected cochlea at post-natal day 15, from either Opa1+/- mice of their wild-type littermates. 4 WT samples, 4 heterozygote samples.
Symbol: Gene expression analysis of the cochlea of Opa1 KO mice
Characterization of Transcriptomes of Apical OHCs and Basal OHCs in Cochlea
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE111302
Tags: unclassified
Summary: We analyzed the transcriptomes of 30 isolated apical OHCs and basal OHCs from rat cochlea, and the results showed that more than 50 genes were differentially expressed and 20 genes were uniquely expressed among these populations. We analyzed these genes with a focus on their functions related to cellular structure and transmembrane channels and their vulnerability to and involvement in hereditary deafness caused by OHC defects. Our results could serve as a guideline for exploring the molecular mechanisms underlying the biological properties of OHCs.
Symbol: Characterization of Transcriptomes of Apical OHCs and Basal OHCs in Cochlea
Ptch1/Shh signaling control cochlear marginal cell differentiation and stria vascularis formation
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE217373
Tags: WT vs. mutant, genotype
Summary: The stria vascularis (SV) is an intricate non-sensory structure composed of multiple cell layers of different origins in the mammalian cochlea. It generates and maintains the endolymph, and therefore is essential for hearing functions. Here, using single cell transcriptomics and transgenic mouse models, we discover that the Shh receptor Ptch1 is required for marginal cell (MC, the epithelial cell layer of SV) differentiation and SV development. During cochlear development, MC differentiation gradually proceeds from cochlear base to apex, resembling the spatiotemporal differentiation pattern of sensory hair cells. Inactivation of Ptch1 leads to an impaired MC differentiation through elevated Gli2 levels, and inhibition of Gli2/Shh signaling activity is a prerequisite for MC differentiation. Single cell transcriptome analyses reveal that MCs are specified as early as E14. Moreover, in the absence of Ptch1, MC precursors are maintained in the progenitor state and differentiation is blocked consequently. Cochleae were dissected out from E16.5 WT and Emx2Cre;Ptch1f/f inner ears, digested into single cell suspension and subjected to 10X Genomics library construction and high-throughput sequencing
Symbol: Ptch1/Shh signaling control cochlear marginal cell differentiation and stria vascularis formation
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-MTAB-3165
Tags: WT vs. mutant, genotype
Summary: RNA was extracted from two Bbs8+/+ and two Bbs8-/- P0 cochlea on separate days allowing for duplicate biological replications of each microarray experiment. RNA was extracted as described previously using the RNAqueous-Microkit (Ambion). Total RNA was further purified on an RNAeasy column (Qiagen) and the RNA quality was checked by an Agilent Bioanalyzer (Agilent Technologies, Palo Alto, CA, USA). Target labeling and hybridization to GeneChips were carried out in the NIDDK Microarray Core facility using the GeneChip Mouse 430_2 Array purchased from Affimetrixs. Samples from each genotype were pooled and split onto two chips each.
Symbol: Affymetrix microarray analysis- Mouse postnatal day cochlea Bbs8 knockout vs Wildtype
Comprehensive transcriptome analysis of cochlear spiral ganglion neurons at multiple ages
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE132925
Tags: baseline, age, developmental stage
Summary: Inner ear cochlear spiral ganglion neurons (SGNs) transmit sound information to the brainstem. Recent single cell RNA-Seq studies have revealed heterogeneities within SGNs. Nonetheless, much remains unknown about the transcriptome of SGNs, especially which genes are specifically expressed in SGNs. To address these questions, we needed a deeper and broader gene coverage than that in previous studies. We performed bulk RNA-Seq on mouse SGNs at five ages, and on two reference cell types (hair cells and glia). Their transcriptome comparison identified genes previously unknown to be specifically expressed in SGNs. To validate our dataset and provide useful genetic tools for this research field, we generated two knockin mouse strains: Scrt2-P2A-tdTomato and Celf4-3xHA-P2A-iCreER-T2A-EGFP. Our comprehensive analysis confirmed the SGN-selective expression of the candidate genes, testifying to the quality of our transcriptome data. These two mouse strains can be used to temporally label SGNs or to sort them. Examination of single cell type at 5 different time points with additional 2 cell types at a single time point for comparison
Symbol: Comprehensive transcriptome analysis of cochlear spiral ganglion neurons at multiple ages
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE196199
Tags: WT vs. mutant, genotype
Summary: The goal of this study is to identify differentially expressed genes in Zbtb20 deleted cochleae. Cochlear mRNA profiles of P10 wild type (WT) and ZB20KO mice
Symbol: Gene expression profiles of wild type and Zbtb20-KO cochleae at P10
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE85519
Tags: WT vs. mutant, genotype
Summary: The Gfi1-Cre mouse is commonly used for conditional hair cell-specific gene deletion/activation in the inner ear. However, we have shown that these mice produce a pattern of recombination that is not strictly limited to hair cells, and that Gfi1cre/+ mice exhibit an early onset progressive hearing loss as compared with their wildtype littermates. Here we performed a transcriptome analysis of Gfi1cre/+ and Gfi1+/+ cochlea to detect potential changes in gene expression that could contribute to their hearing loss phenotype, or that could potentially confound downstream analysis of conditional gene deletion using these mice. Trancriptome profiles of P8 cochlear duct from mice of two genotype - Gfi1cre/+ and Gfi+/+ controls - were measured. Gene expression levels were recorded in independent triplicates using polyA-enriched RNA-seq
Symbol: Expression profiling of cochlear ducts from P8 Gfi1cre/+ and Gfi1+/+ mice
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-4786, GEO:GSE4786
Tags: baseline, age
Summary: Presbycusis is characterized by an age-related progressive decline of auditory function, and arises mainly from the degeneration of hair cells or spiral ganglion (SG) cells in the cochlea. Here we show that caloric restriction suppresses apoptotic cell death in the mouse cochlea and prevents late onset of presbycusis. Caloric restricted mice, which maintained body weight at the same level as that of young control (YC) mice, retained normal hearing and showed no cochlear degeneration. CR mice also showed significantly fewer TUNEL-positive staining cells and fewer cleaved caspase-3-positive staining cells relative to middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated the expression of 28 proapoptotic genes, including Bak and Bim. Taken together, our findings suggest that loss of critical cells through apoptosis is an important mechanism of presbycusis in mammals, and that CR or staying lean can retard this process by suppressing apoptosis in the inner ear tissue. Experiment Overall Design: To examine the effects of aging, a comparison of cochlea tissues from YC (3 samples) and MC (3 samples) mice was conducted. To examine the effects of calorie restriction (CR), a comparison of cochleae from MC (3 samples) and CR (3 samples) mice was conducted. We examined age-related changes in gene expression in the cochlea and calorie restriction-induced changes in gene expression in the cochlea. We pooled four cochleae from two mice for one sample and used three samples per group (n = 3). Quality control measures were not used. No replicates were done. Dye swap was not used.
Symbol: Transcription profiling by array of cochleae from mice fed a calorie-restricted diet
Transcriptomes of control and Chd7-deficient spiral ganglia neurons and cochlear hair cells
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE163798
Tags: WT vs. mutant, anatomical structure, genotype
Summary: The aim of this study is to identify the gene targets of Chd7 (by RNA-seq) in spiral ganglia neurons and cochlear hair cells. mRNA profiles of FACS-sorted spiral ganglia neurons from 4-day old mice and cochlear hair cells from embryos af 16.5 days in controls, Chd7 heterozygous and Chd7 homozygous mutant animals were generated by paired-end sequencing, in triplicate, using Illumina HiSeq 4000. The sequence reads that passed quality filters were reads were aligned to mouse MM10 genome assembly using HiSAT2 (version 2.1.0) with the default parameters in Galaxy (version 2.1.0). To facilitate quantitative gene expression analysis, aligned reads for each sample were counted using featureCounts (version1.6.4). Differential gene expression analysis was performed using DESeq2 (version 2.11.40.6), applying parametric fit. qRTâPCR validation was performed using SYBR Green and gene specific primers. To identify differentially expressed genes, RPKM values of genes that are not normally expressed in E16.5 hair cells or P4 spiral ganglia neurons were removed from analysis. This resulted in 6910 transcripts for genes expressed in hair cells and 11293 genes expressed in neurons. A pairwise comparison between controls and homozygotes and controls and heterozygotes was performed. Significant thresholds were considered for transcripts with an adjusted p-value (FDR) of <=0.05 and linear fold change of >2 in either direction. Altered expression of selected genes was confirmed with qRT-PCR as well as the encoded proteins by immunohistochemistry. Analysis of differentially expressed genes uncovered novel targets and potential mechanisms by which Chd7 controls the survival of these cells during normal hearing. Hair cell mRNA profiles of embryonic day (E) 16.5 Atoh1Cre;mTmG control (CTRL), Atoh1Cre;Chd7f/+;mTmG heterozygous (HET) and Atoh1Cre;Chd7f/+;mTmG heterozygous (HOM) mice. Neuronal mRNA profiles of 4-day old NeuroD1Cre;mTmG control (CTRL), NeuroD1Cre;Chd7f/+;mTmG heterozygous (HET) and NeuroD1Cre;Chd7f/+;mTmG heterozygous (HOM) mice.
Symbol: Transcriptomes of control and Chd7-deficient spiral ganglia neurons and cochlear hair cells
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-35234, GEO:GSE35234
Tags: baseline, age
Summary: Gene expression within the cochlea of C57BL6j mice was examined. The hypothesis was that there was a genetic component to Age Related Hearing Loss and microarray would be useful in detecting candidate genes. Mice were aged in the laboratory to 4, 15 and 45 weeks of age. The cochlea were removed and pooled into groups of 5 for each age group. Total RNA was extracted and used in the micoroarray analysis. Differential expression was analysed between the different age groups i.e 4 - 15, 4 - 45 and 15 - 45 weeks.
Symbol: Analysis of the gene expression within the cochlea of aging C57BL6j mice
Gene expression profiles along the tonotopic axis of the mouse cochlea during neonatal development
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-34187, GEO:GSE34187
Tags: anatomical structure, baseline, developmental stage
Summary: The cochlear duct is tonotopically organized, such that the basal cochlea responds more sensitively to high frequency sounds and the apical cochlea to low frequency sounds. In effort to understand how the tonotopic organization is established in mammals, we searched for genes that are differentially expressed along the tonotopic axis during neonatal development. Eighty temporal bones were dissected from C57BL/6 mice at P0 and P8. The cochlear tissues were divided into three equal pieces representing the basal, middle and apical turns, and pooled separately. Six total RNA from the pooled samples were applied to 6 GeneChips.
Symbol: Gene expression profiles along the tonotopic axis of the mouse cochlea during neonatal development
Genome-wide enhancer profiling identifies novel Shh regulated gene targets in the developing cochlear duct
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE131165
Tags: WT vs. mutant, genotype
Summary: The development of the mammalian inner ears is a highly dynamic process that is dependent on the interplay of multiple signaling molecules. Previous studies demonstrated the role of Shh in the initiation and outgrowth of the cochlea. However, the gene targets of Shh in the cochlea largely remain unknown. We show in this study, Shh responsive genes that are loss in the cochlea of Smoecko mutant (Smo null) and upregulated in Shh-P1 mutant embryos through comparative RNA-seq profiling. We performed a genome-wide cis-regulatory element (cRE) study (via ATAC-seq and Gli2 ChIP-seq) and identified potential cREs that are targets of the Shh signaling pathway in the cochlea. Our data unravel novel Shh signaling regulated gene targets that have important functional roles in the development of the cochlea. 1) Examination of genome wide gene expression in 2 different inner ear mutants at E11.5, 2) Examination genome wide of open chromatin regions using ATAC-seq in E11.5 inner ear, 3) Examination of genome wide Gli2 binding site in the E10.5 embryonic head
Symbol: Genome-wide enhancer profiling identifies novel Shh regulated gene targets in the developing cochlear
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-32963, GEO:GSE32963
Tags: baseline, developmental stage
Summary: To understand the molecular control of development and regeneration in the mammalian cochlear sensory epithelia, we performed a comparative study of gene expression patterns between postnatal day-3 (P3) and adult stages using a microarrays approach. Two inner ear development stages were used in this study, Post-natal day three and eight-week-old adult. A total number of sixty Swiss mice were exploited for each stage. The cochlear sensory epithelia (CSE) were collected from the inner ears and immediately placed in RNA later solution. A total of six independent dissection experiments were carried out separately in order to obtain three biological replicates for each stage. In each experiment, the CSE from 20 mice were pooled. Total RNA was purified from each biological sample separately using RNAeasy Mini Kit and the RNA integrity was assessed by the Nanodrop 2000
Symbol: Gene expression profile in the developing and adult mouse cochlear sensory epithelia
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-53863, GEO:GSE53863
Tags: anatomical structure, baseline
Summary: This study demonstrates the baseline data of gradient gene expression in the cochlea. Especially for genes whose mutations cause autosomal dominant non syndromic hearing loss (Pou4f3, Slc17a8, Tmc1, and Crym) as well as genes important for cochlear function (Emilin-2 and Tectb), gradual expression changes help to explain the various pathological conditions. Four C57BL/6 mice aged 6 weeks cochlea samples including the lateral wall, stria vascularis, spiral ligament, spiral prominence, and the organ of corti were dissected and separated into the apical, middle and basal turns to compare gene expression profiles of each cochlea turn.
Symbol: Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis
The single-cell transcriptional landscape of neuronal fates in the developing mouse cochlea
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE165502
Tags: baseline, developmental stage
Summary: The spiral ganglion neurons (SGNs) of the cochlea are essential for auditory perception by transmitting complex auditory information from hair cells (HCs) to the brain, yet the molecular mechanisms generating their diversity are unknown. Here we used single cell RNA sequencing to reconstruct the developmental trajectories of SGN cell fates and identified genes and gene regulatory networks that participate to changes in developmental competence and cell states, and in specification of each major cell types. Our analysis also identified gene modules associated with the sequential binary decisions that delineate neuron fate choices along the diversification tree. Transcriptome analysis of both developing SGN and HC types further revealed cell-state specific cell-cell signaling potentially playing a role in the differentiation and connectivity profile of SGNs as well as human deafness-associated genes, both previously known and novel. Overall, our results identify molecular principles that shape SGN differentiation and will facilitate further studies of SGNs development, physiology and dysfunction. Smart-Seq2 protocol was performed on single isolated cells by Eukaryotic Single Cell Genomics Facility at SciLifeLab, Stockholm. From the Ntrk3Cre;R26tdTOM E14.5 samples, we isolated a total of 135 cells, including 82 neurons and 53 OM. From the PVcre;R26tdTOM mice we isolated a total of 2139 cells: 229 at E15.5 (161 neurons and 68 OM), 661 at E16.5 (580 neurons and 73 OM and 8 HCs), 72 at E17.5 (71 neurons and 1 HC) and 667 at E18.5 (611 neurons and 66 HC). The P3 the transcriptional data was obtained from our previous study.
Symbol: The single-cell transcriptional landscape of neuronal fates in the developing mouse cochlea
Comparison of wildtype and Fmr1 knock-out adult mouse gene expression in the cochlear nucleus
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE236056
Tags: WT vs. mutant, genotype
Summary: Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the Fmr1- knock-out (KO) mouse model for FXS exhibits auditory seizures. FMRP is strongly expressed in the cochlear nucleus and other auditory brainstem nuclei. We hypothesize that the Fmr1-KO mouse has altered gene expression in the cochlear nucleus that may contribute to auditory hypersensitivity. Cochlear nuclei (containing both ventral and dorsal portions) were dissected from Fmr1-KO and WT mice (n=3 each), at age two months. Gene expressions were compared between the two genotypes.
Symbol: Comparison of wildtype and Fmr1 knock-out adult mouse gene expression in the cochlear nucleus
The impact of Prdm16 deletion on the transcriptome of the developing cochlear duct cells
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE193046
Tags: WT vs. mutant, genotype
Summary: The PR domain containing 16 (PRDM16) is a key transcription regulator in the development of craniofacial, adipose, neural, and hematopoietic tissues. Our lab identified PRDM16 expression in the epithelial cells of the Kolliker's organ (KO) starting around E13.5 and maintained until the disappearance of the KO around P10. Bulk RNA sequencing of cochlear duct cells at E14.5 followed by quantitative real time PCR and mRNA Fluorescence in-situ hybridization identified differentially expressed genes in Prdm16-null versus littermate control cochleae.
Symbol: The impact of Prdm16 deletion on the transcriptome of the developing cochlear duct cells
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE233706
Tags: baseline
Summary: The research on the regulation mechanism of gene expression during cochlear development provides a basis for regenerative medicine. Single-cell multi-omics sequencing integrating ATACs and gene expression is a powerful tool for exploring gene expression regulatory networks.
Symbol: Single Cell Multiome (ATAC + Gene Expression) sequencing of mouse cochlea at E12.5
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE149916
Tags: WT vs. mutant, genotype
Summary: The aim of this study consists in detecting genes regulated by Meis2 in the murine cochlea In this data set we present 256 genes differentially regulated by Meis2 in the murine cochlea. These data serve as a platform for verifying their differential regulation by Meis2 via RNA in situ hybridisation or qPCR 4 Total samples were analyzed. A pairwise comparison between two wild-type and 2 Meis2 mutants samples was conducted. Genes with a FDR<0.05 are presented.Briefly, the robust microarray analysis (RMA) algorithm was used for background correction, intra- and inter-microarray normalization, and expression signal calculation. Once the absolute expression signal for each gene (i.e., the signal value for each probe set) was calculated in each microarray, a method [called significance analysis of microarray (SAM)] was applied to calculate significant differential expression and find the gene probe sets that characterized the highly metastatic samples. The method uses permutations to provide robust statistical inference of the most significant genes and provides P valuesadjusted to multiple testing using false discovery rate (FDR).
Symbol: Expression data from cochlea isolated from Meis2 mutant and wild-type mice at E15
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-61406, GEO:GSE61406
Tags: WT vs. mutant, genotype
Summary: The aim of this study consists in detecting genes regulated by N-myc in the murine cochlea In this data set we present 2688 genes differentially regulated by Nmyc in the murine cochlea. These data serve as a platform for verifying their differential regulation by N-myc via RNA in situ hybridisation or other techniques. 4 Total samples were analyzed. A pairwise comparison between two wild-type and 2 N-myc mutants samples was conducted. Genes with a FDR up to 14% are presented. Briefly, the robust microarray analysis (RMA) algorithm was used for background correction, intra- and inter-microarray normalization, and expression signal calculation. Once the absolute expression signal for each gene (i.e., the signal value for each probe set) was calculated in each microarray, a method [called significance analysis of microarray (SAM)] was applied to calculate significant differential expression and find the gene probe sets that characterized the highly metastatic samples. The method uses permutations to provide robust statistical inference of the most significant genes and provides P valuesadjusted to multiple testing using false discovery rate (FDR).
Symbol: Expression data from cochlea isolated from N-myc mutant and wild-type mice at E15
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE203228
Tags: WT vs. mutant, genotype
Summary: To show that FST cooperates with SHH to establish tonotopy by promoting apical cochlear characteristics responsible for low-frequency hearing in mammals, we analyzed cochlear gene expression, morphology, and auditory function of mouse mutants with loss or gain of SHH function in combination with loss or gain of follistatin (FST) function. Gene expression profiling analysis of RNA-seq data for 4-week-old control and Fst conditional Knock-out mutant mice cochlea cells divided into three regions along the tonotopic axis, base, middle, and apex.
Symbol: Follistatin regulates sonic hedgehog-dependent tonotopic organization of the apical cochlea responsible
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-18567, GEO:GSE18567
Tags: WT vs. mutant, age, developmental stage, genotype
Summary: Efferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit. Cochleae were removed at postnatal ages P3, P7, P13 and P60. Cochlear tissues from 3-5 mice were pooled per replicate; biological triplicates were performed for each age and genotype.
Symbol: Temporal profiling of gene expression in cochleae of wild type and alpha9 null mice
ESRP1 mutations cause hearing loss due to defects in alternative splicing that disrupt cochlear development
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE90821
Tags: WT vs. mutant, genotype
Summary: Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing Regulatory Protein 1 (ESRP1). Patient derived induced pluripotent stem cells showed alternative splicing defects consistent with impaired ESRP1 function. To determine how mutations in ESRP1 cause hearing loss we evaluated Esrp1-/- mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation and cell fate specification. Transcriptome analysis revealed impaired expression and splicing of genes with essential roles in inner ear development and auditory function. In particular, aberrant splicing of Fgfr2 blocked stria vascularis formation due to erroneous ligand usage, which was corrected by reducing Fgf9 gene dosage. These findings implicate mutations in ESRP1 as a novel cause of SNHL and demonstrate the complex interplay between alternative splicing, inner ear development, and auditory function. 3 biological replicates of whole E16.5 cochlear epithelium from individual Esrp1+/+ (Control) and Esrp1-/- (E1-KO) embryos (2 cochlea pooled from each embryo) were analyzed by RNA-seq
Symbol: ESRP1 mutations cause hearing loss due to defects in alternative splicing that disrupt cochlear development
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE148380
Tags: WT vs. mutant, genotype
Summary: Background: Understanding the developmental mechanisms that regulate hair cell differentiation in the cochlea is essential to designing genetic therapies for acquired hearing loss due to hair cell loss or damage. We have previously identified Fibroblast Growth Factor 20 (FGF20) as having a key role in hair cell and supporting cell differentiation and patterning in the mouse cochlear sensory epithelium. To investigate the genetic landscape regulated by FGF20 signaling in hair cell and supporting cell progenitors, we employ Translating Ribosome Affinity Purification (TRAP) combined with Next Generation mRNA Sequencing (TRAPseq). Methods: In mice, we used Fgf20-Cre to activate ROSA-fsTRAP in hair cell and supporting cell progenitors, and then collected translating mRNA using TRAP from Fgf20+/- (control) and Fgf20-/- cochleae. Library preparation and sequencing were done in two separate experiments, each with 12 samples that included 2 pre-TRAP (pre-immunoprecipitation) Fgf20+/- samples, 2 TRAP Fgf20+/- samples, 4 pre-TRAP Fgf20-/- samples, and 4 TRAP Fgf20-/- samples. Samples were sequenced via Illumina HiSeq 3000. We compared pre-TRAP (pre-immunoprecipitation) samples with TRAP mRNA samples to validate the TRAP technique as well as identify genes enriched in our target cell population. We also compared Fgf20+/- and Fgf20-/- TRAP mRNA samples to identify differentially expressed genes downstream of FGF20 during hair cell and supporting cell differentiation. Results: TRAPseq targeting the prosensory cell population effectively enriches for translating mRNA within this rare cell population. TRAPseq comparing Fgf20+/- and Fgf20-/- samples identified differentially expressed genes downstream of FGF20. These included FGF-response genes Etv4, Etv5, Etv1, and Dusp6, as well as genes associated with cochlea development and hearing, such as Hey1, Hey2, Heyl, Tectb, Fat3, Cpxm2, Sall1, and cell cycle regulators such as Cdc20. E14.5 cochlear mRNA collected with translating ribosome affinity purification from Fgf20+/- and Fgf20-/- mouse cochleae. Expression of L10a-eGFP protein was targeted to the Fgf20-Cre lineage. Each sample is pooled from 3-7 embryos of the same genotype.
Symbol: Analysis of FGF20-regulated genes in differentiating cochlear hair and supporting cell progenitors via
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE221546
Tags: anatomical structure, baseline, developmental stage
Summary: To study and compare the genes and miRNA expression during the development of the Organ of Corti and the Superior Olivary complex, representing the peripheral and the central auditory systems. We extracted RNA and small RNA from these two organs at 3 important developmental time points and performed bioinformatical analysis of the expression.
Symbol: Shared and organ-specific gene-expression programs during the development of the cochlea and the superior
Noise-Induced Changes in Gene Expression in the Cochleae of Mice Differing in Their Susceptibility to Noise Damage
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-8342, GEO:GSE8342
Tags: strain study, baseline
Summary: The molecular mechanisms underlying the great differences in susceptibility to noise-induced hearing loss (NIHL) exhibited by both humans and laboratory animals are unknown. Using microarray technology, the present study demonstrates that the effects of noise overexposure on the expression of molecules likely to be important to the development of NIHL differ among inbred mice that have distinctive susceptibilities to NIHL including B6.CAST, 129X1/SvJ, and 129S1/SvImJ. The noise-exposure protocol produced, on average, a permanent loss of about 40 dB in sensitivity for auditory brainstem responses in susceptible B6.CAST mice, but no threshold elevations for the two resistant 129S1/SvImJ and 129X1/SvJ substrains. Measurements of noise-induced gene expression changes 6 h after the noise exposure revealed significant alterations in the expression levels of 48 genes in the resistant mice, while by these same criteria, there were seven differentially expressed genes in the susceptible B6.CAST mice. Differentially expressed genes in both groups of mice included subsets of transcription factors. However, only in the resistant mice was there a significant induction of proteins involved in cell-survival pathways such as HSP70, HSP40, p21, GADD45beta, Ier3, and Nf-kappaB. Moreover, increased expression of three of these factors after noise was confirmed at the protein level. Drastically enhanced HSP70, GADD45beta, and p21 immunostaining were detected 6 h after the noise exposure in subsets of cells of the lateral wall, spiral limbus, and organ of Corti as well as in cochlear nerve fibers. Upregulation of these proteins after noise exposure likely contributes to the prevalence of survival cellular pathways and thus to the resistance to NIHL that is characteristic of the 129X1/SvJ mice. Experiment Overall Design: Female 10-wk-old mice of the B6.CAST and 129X1/SvJ strains were divided randomly into non-noise control and noise-exposure groups. The non-noise mice served as controls in the gene-profiling experiments to control for the stress induced by experimenter handling and/or confinement of the mice in the noise-exposure chamber that was not directly related to the noise. This mice were in the noise chamber for a sham exposure. In contrast, the "noise" groups were exposed to a 105-dB SPL, 10-kHz octave band of noise for 1 h and sacrificed 6 h after the exposure. Of each of these major groups, eight mice were used for each of three 129X1/SvJ control and three noise-exposed 129X1/SvJ arrays and two B6.CAST control and two noise-exposed B6.CAST arrays. Consequently within each subgroup the arrays are biological replicates.
Symbol: Noise-Induced Changes in Gene Expression in the Cochleae of Mice Differing in Their Susceptibility to
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE221545
Tags: anatomical structure, baseline, developmental stage
Summary: To study and compare the genes and miRNA expression during the development of the Organ of Corti and the Superior Olivary complex, representing the peripheral and the central auditory systems. We extracted RNA and small RNA from these two organs at 3 important developmental time points and performed bioinformatical analysis of the expression and performed bioinformatical analysis of the expression.
Symbol: Shared and organ-specific gene-expression programs during the development of the cochlea and the superior
Single-cell RNA sequencing analysis reveals Greater Epithelial Ridge cells degeneration during postnatal development of cochlea in Rats
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE170810
Tags: unclassified
Summary: Greater epithelial ridge cells, atransientneonatalcell group in the cochlear duct, which plays a crucial role in the functional maturation of hair cell, structural development of tectorial membrane, and refinement of audio localization before hearing. Greater epithelial ridge cells are methodologically homogeneous, while whether different cell subtypes are existence in this intriguing region and the degeneration mechanism during postnatal cochlear development are poorly understood. In the present study, single-cell RNA sequencing was performed on the cochlear duct of postnatal rats at day 1 (P1) and day 7 (P7) to identify subsets of greater epithelial ridge cell and progression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to examine genes enriched biological processes in these clusters. We identified a total of 26 clusters at P1 and P7 rats and found that the cell number of five cell clusters decreased significantly, while four clusters had similar gene expression patterns and biological properties. The genes of these four cell populations were mainly enriched in Ribosome and P13K-Akt signal pathway. Among them, Rps16, Rpsa, Col4a2, Col6a2, Ctsk, and Jun are particularly interesting as their expression might contribute to the greater epithelial ridge cells degeneration. In conclusion, our study provides an important reference resource of greater epithelial ridge cells landscape and mechanism insights for further understanding greater epithelial ridge cells degeneration during postnatal rat cochlear development
Symbol: sequencing analysis reveals Greater Epithelial Ridge cells degeneration during postnatal development of cochlea
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-26822, GEO:GSE26822
Tags: WT vs. mutant, anatomical structure, genotype
Summary: Cre recombinase-mediated conditional knockout of floxed Dicer1 alleles causes depletion of small RNAs including microRNAs, which function to repress target mRNA expression by inhibiting translation and/or stimulating mRNA degradation. We used microarrays to examine gene expression in apical versus basal organ of Corti from the cochleae of control and mutant mice in which Dicer1 was deleted and microRNAs were depleted specifically in sensory hair cells by Atoh1 promoter-driven Cre recombinase expression. Each biological replicate represents the combined apical or combined basal segments of organ of Corti from both cochleae of a single mouse. Two biological replicates for apical and basal organ of Corti from Dicer1 conditional knockout and littermate controls were collected for RNA extraction and microarray analysis.
Symbol: postnatal mouse apical and basal organ of Corti from Dicer1 conditional knockout and littermate control cochleae
Characterization of Rare Spindle and Root Cell Transcriptional Profiles in the Stria Vascularis of the Adult Mouse Cochlea
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE152551
Tags: baseline
Summary: snRNA-Seq using sample preservation distinguishes rare spindle and root cell transcriptional profiles 2 samples, Stria vascularis dissected from adult CBA/J mice per experiment Grant information: ZIA DC000088-05
Symbol: Characterization of Rare Spindle and Root Cell Transcriptional Profiles in the Stria Vascularis of the Adult Mouse Cochlea
The upregulation of K+ and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE242669
Tags: baseline, genotype
Summary: Spiral ganglion neurons (SGNs) are primary sensory afferent neurons that relay acoustic information from the cochlear inner hair cells (IHCs) to the brainstem. The response properties of different SGNs diverge to represent a wide range of sound intensities in an action-potential code. This biophysical heterogeneity is established during pre-hearing stages of development, a time when IHCs fire spontaneous Ca2+ action potentials that drive glutamate release from their ribbon synapses onto the SGN terminals. The role of spontaneous IHC activity in the refinement of SGN characteristics is still largely unknown. Using pre-hearing otoferlin knockout mice (Otof-/-), in which Ca2+-dependent exocytosis in IHCs is abolished, we found that developing SGNs fail to upregulate low-voltage-activated K+-channels and hyperpolarisation-activated cyclic-nucleotide-gated channels. This delayed maturation resulted in hyperexcitable SGNs with immature firing characteristics. We have also shown that SGNs that synapse with the pillar side of the IHCs selectively express a resurgent K+ current, highlighting a novel biophysical marker for these neurons. RNA-sequencing showed that several K+ channels are downregulated in Otof-/- mice, further supporting the electrophysiological recordings. Our data demonstrate that spontaneous Ca2+-dependent activity in pre-hearing IHCs regulates some of the key biophysical and molecular features of the developing SGNs. KEY POINTS: Ca2+-dependent exocytosis in inner hair cells (IHCs) is otoferlin-dependent as early as postnatal day 1. A lack of otoferlin in IHCs affects potassium channel expression in SGNs. The absence of otoferlin is associated with SGN hyperexcitability. We propose that type I spiral ganglion neuron functional maturation depends on IHC exocytosis. Cochlear Tissue was dissected from heterozygous and homozygous otof KO mice and submitted for RNA-sequencing. Both pairs of cochleas from 2-3 P7 pups were pooled for each genotype. (n=2 pools per genotype). Samples were dissected in the same manner as used for all patching experiments. RNA-seq data was analyzed using the nf-core pipeline and differential expression testing was performed using DeSEQ2.
Symbol: The upregulation of K+ and HCN channels in developing spiral ganglion neurons is mediated by cochlear
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-6196, GEO:GSE6196
Tags: baseline
Summary: The goal was to screen for the expressed genes in Reissner's membrane (RM) that are related to ion transport and its regulation. The objectives were 1) to determine whether short-term incubation altered the transcriptome and 2 ) to discover which genes changed expression levels in response to glucocorticoids. Experiment Overall Design: RM was dissected free-hand from mouse cochleae and either immediately subjected to RNA extraction or incubated for 24 as explants. Two series of samples were incubated in the presence or absence of dexamethasone (100 nM) and samples of RM were pooled to obtain sufficient material for gene array analysis. The pooled samples were used to hybridize 3 gene array chips for each biological sample.
Symbol: Transcription profiling of mouse cochlea Reissners membrane grown as explants and treated with dexamethasone
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE217727
Tags: baseline, developmental stage
Summary: Otic Mesenchyme Cells (OMCs) are the numerous cell type during cochlear development. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of OMCs during cochlear development
Symbol: Gene expression profiles at the single cell level of cochlear cells from C57BL/6J mice at both embryonic