RNA expression data of inner ear tissues in SOX10 p.R109W mutation pigs with inner ear malformation and wild-type pigs
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PROVIDER: PRJNA432847 | ENA |
REPOSITORIES: ENA
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Project description:SOX10 (SRY-box 10) mutation may lead to inner ear deformities. However, its molecular mechanisms on inner ear development are not clear. In this work. The inner ear morphology was investigated at different embryonic stages of the SOX10 mutation miniature porcine model with sensorineural hearing loss, and high-throughput RNA-seq and bioinformatics analyses were applied. Our results indicated that the SOX10 mutation in the miniature pigs led to an incomplete partition of the cochlea, a cystic apex caused by fusion from middle and apical turns, cochlear modiolar defects and a shortened cochlear duct. The model demonstrated 173 DEGs and 185 lncRNAs. The down-regulated DEGs most significantly enriched the inflammatory mediator regulation of the TRP channels, arachidonic acid metabolism, and the salivary secretion pathways, while the up-regulated DEGs most significantly enriched the systemic lupus erythematosus and alcoholism pathways. Based on gene cluster analysis, we selected four gene groups: WNT1, KCNQ4, STRC and PAX6.
2018-06-21 | GSE110103 | GEO
Project description:The embryonic endolymphatic sac mediates fluid resorption for which anion exchangers such as SLC26A4, and its transcriptional activator FOXI1, are required. Apart from FOXI1, little is known about transcriptional regulators of this fluid balance. Altered fluid homeostasis in the inner ear is the leading cause of congenital hearing loss. Some patients with campomelic dysplasia (CD) caused by heterozygous mutations in SOX9, in addition to skeletal malformation, are deaf, with an unknown etiology. In a mouse model of CD caused by the SOX9Y440X mutation, which results in a truncated protein lacking the transactivation domain, we show severe endolymphatic dysfunction leading to deafness and vestibular problems. Adult heterozygous Sox9Y440X mice that express the mutation in the developing inner ear display sensorineural deafness combined with endolymphatic hydrops and lack of endocochlear potential. The mutant inner ear is enlarged from E15 and fewer Slc26a4-expressing cells are present in the endolymphatic epithelium. By single cell RNA sequencing of mutant and wild-type endolymphatic sacs we find marked reduction in genes important for ion transport such as Slc24a4 and Ttyh1 and gap-junctions such as Gjb2 and up-regulation of Wnt signaling and Igfbp2 that promotes progenitor proliferation. The cochlea overexpresses Aqp3, which encodes a water channel. We find by biochemical and cell-based transactivation assays and genetic interaction tests that SOX9 and SOX10 normally work co-operatively to repress Aqp3 transcription: SOX9Y440X blocks this repression by dominant interference. Our study reveals the key roles of SOXE transcription factors in the development of endolymphatic sac function, and highlight a molecular mechanism whereby the CD mutation exerts both a dominant negative and haploinsufficient mechanisms in different compartments of the inner ear to maintain fluid homeostasis. In the cochlea, SOX9 and SOX10 together repress aquaporin expression whereas in the endolymphatic sac, SOX9 controls SOX10 expression and genes for ion transport and gap-junctions. We postulate that in addition to loss of control of cell proliferation results in the exhaustion of progenitors which in turn leads to a deficit in mitochondria-rich cells. These results highlight a multifaceted mechanism for maintaining the proper fluid balance for hearing.
2022-10-10 | GSE131196 | GEO
Project description:The embryonic endolymphatic sac mediates fluid resorption for which anion exchangers such as SLC26A4, and its transcriptional activator FOXI1, are required. Apart from FOXI1, little is known about transcriptional regulators of this fluid balance. Altered fluid homeostasis in the inner ear is the leading cause of congenital hearing loss. Some patients with campomelic dysplasia (CD) caused by heterozygous mutations in SOX9, in addition to skeletal malformation, are deaf, with an unknown etiology. In a mouse model of CD caused by the SOX9Y440X mutation, which results in a truncated protein lacking the transactivation domain, we show severe endolymphatic dysfunction leading to deafness and vestibular problems. Adult heterozygous Sox9Y440X mice that express the mutation in the developing inner ear display sensorineural deafness combined with endolymphatic hydrops and lack of endocochlear potential. The mutant inner ear is enlarged from E15 and fewer Slc26a4-expressing cells are present in the endolymphatic epithelium. By single cell RNA sequencing of mutant and wild-type endolymphatic sacs we find marked reduction in genes important for ion transport such as Slc24a4 and Ttyh1 and gap-junctions such as Gjb2 and up-regulation of Wnt signaling and Igfbp2 that promotes progenitor proliferation. The cochlea overexpresses Aqp3, which encodes a water channel. We find by biochemical and cell-based transactivation assays and genetic interaction tests that SOX9 and SOX10 normally work co-operatively to repress Aqp3 transcription: SOX9Y440X blocks this repression by dominant interference. Our study reveals the key roles of SOXE transcription factors in the development of endolymphatic sac function, and highlight a molecular mechanism whereby the CD mutation exerts both a dominant negative and haploinsufficient mechanisms in different compartments of the inner ear to maintain fluid homeostasis. In the cochlea, SOX9 and SOX10 together repress aquaporin expression whereas in the endolymphatic sac, SOX9 controls SOX10 expression and genes for ion transport and gap-junctions. We postulate that in addition to loss of control of cell proliferation results in the exhaustion of progenitors which in turn leads to a deficit in mitochondria-rich cells. These results highlight a multifaceted mechanism for maintaining the proper fluid balance for hearing.
2022-10-10 | GSE139587 | GEO
Project description:Waardenburg syndrome (WS) is a autosomal dominant inherited disorder characterized by sensorineural hearing loss (SNHL) and pigment abnormalities. SOX10 is one of its main pathogenicity genes. In vitro generation of patient-specific induced pluripotent stem cells (iPSCs) is an effective approach for exploring the mechanisms of human disease. Here, we established an iPSCs from a WS patient with SOX10 mutation and differentiated it into induced neural crest cells (NCCs), the key cell type involves in inner ear development. Compared with control-derived iPSCs, the SOX10 mutant iPSCs showed significantly decreased efficiency of development and differentiation potential at the stage of NCCs. We then performed high-throughput RNA-seq and examined the transcriptional misregulation at each stage. The transcriptome analysis differentiated NCCs reveals widespread gene expression changes and the differentially expressed genes(DEGs) were enriched with gene ontology (GO) of neuron migration, skeletal system development, multicellular organism development, which indicate the important role of SOX10 plays in the differentiation of NCCs. It's worth noting that, a significant enrichment among the nominal DEGs for genes implicated in inner ear development was found, as well as several genes related to the inner ear morphogenesis. Based on protein-protein interaction（PPI）net work, we selected four candidate genes that may be regulated by SOX10 in inner ear development: BMP2, LGR5, GBX2 and GATA3. In conclusion, the SOX10 deficiency in this WS patient has a significant impact on the gene expression patterns during the development of NCCs. The DEGs most significantly enriched the inner ear development and morphogenesis could help explain the underlying basis for the inner ear malformation seen in WS patient.
2021-06-04 | GSE176101 | GEO
Project description:The inner ear continues to grow and develop until the auditory and vestibular systems reach full maturity and all of the genes involved in this process have yet to be identified. Previous gene based analysis have primarily focused on the early developmental stages following induction and initial formation of the inner ear. The aim of this study is to identify new candidate genes for inner ear development. Microarrays were used to produce expression profiles from larval stages 56,57,58 of the Xenopus laevis inner ear. The data produced from this work represent an annotated resource that can be utilized by the Xenopus community to provide candidates for further functional analysis. Xenopus inner ears were isolated from larval animals for RNA extraction and hybridization to Affymetrix GeneChip microarrays.
2016-02-29 | E-GEOD-73829 | biostudies-arrayexpress
Project description:The inner ear continues to grow and develop until the auditory and vestibular systems reach full maturity and all of the genes involved in this process have yet to be identified. Previous gene based analysis have primarily focused on the early developmental stages following induction and initial formation of the inner ear. The aim of this study is to identify new candidate genes for inner ear development. Microarrays were used to produce expression profiles from larval stages 50,51,52 of the Xenopus laevis inner ear. The data produced from this work represent an annotated resource that can be utilized by the Xenopus community to provide candidates for further functional analysis.
2016-12-31 | GSE73828 | GEO
Project description:The inner ear continues to grow and develop until the auditory and vestibular systems reach full maturity and all of the genes involved in this process have yet to be identified. Previous gene based analysis have primarily focused on the early developmental stages following induction and initial formation of the inner ear. The aim of this study is to identify new candidate genes for inner ear development. Microarrays were used to produce expression profiles from larval stages 56,57,58 of the Xenopus laevis inner ear. The data produced from this work represent an annotated resource that can be utilized by the Xenopus community to provide candidates for further functional analysis.
2016-02-29 | GSE73829 | GEO
Project description: Not available
| S-EPMC5996026 | biostudies-literature
Project description:We implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis. Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. Gene expression analysis of Xenopus laevis juvenile inner ear tissue. Inner ear RNA isolated from three groups of 5-10 juvenile X. laevis. Each biological replicate represents pooled inner ear RNA from 10-19 inner ears.
2012-05-04 | E-GEOD-37767 | biostudies-arrayexpress
Project description:Objective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition. Methods: To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes. Results: Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear. Conclusion: Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media. There are 6 control samples and 8 samples trans-tympanically injected with H flu 10e9 for 6 hours. Each sample is a pool of 4 animals
2013-07-23 | E-GEOD-49122 | biostudies-arrayexpress