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Open chromatin in Sox2-EGFP-sorted cells of the embryonic mouse cochlear duct

ABSTRACT: Open chromatin in Sox2-EGFP-sorted cells of the embryonic mouse cochlear duct

PROVIDER: PRJNA544803 | ENA |

REPOSITORIES: ENA

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Open chromatin in Sox2-EGFP-sorted cells of the embryonic mouse cochlear duct

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.

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Transcripts identified by microarray analysis that were deregulated in E14.5 Sox2(creERT2);Tbx2(fl/fl) (Sox2-Tbx2LOF) cochlear duct.

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Project description: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 totoal 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.

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MicroRNAs Involved in Aging of the Lateral Wall of the Cochlear Duct

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The impact of Prdm16 deletion on the transcriptome of the developing cochlear duct cells

Project description: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 Kölliker’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.

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The cells of the sensory epithelium, and not the stria vascularis, are the main cochlear cells related to the genetic pathogenesis of age-related hearing loss

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Genome-wide enhancer profiling identifies novel Shh regulated gene targets in the developing cochlear duct

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