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

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

PROVIDER: PRJNA542806 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9051760.fastq.gz	Fastqsanger.gz
	SRR9051770_1.fastq.gz	Fastqsanger.gz
	SRR9051770_2.fastq.gz	Fastqsanger.gz
	SRR9051761.fastq.gz	Fastqsanger.gz
	SRR9051771_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

2019-09-09 | GSE131165 | GEO

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

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

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

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

2014-10-01 | GSE57782 | GEO

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.

2022-07-01 | GSE193046 | GEO

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

Project description:Evaluation of transcriptional changes in the E14.5 cochlear duct epithelium upon tamoxifen-induced loss of Tbx2 in prosensory cells.

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Ptch1/Shh signaling control cochlear marginal cell differentiation and stria vascularis formation

Project description: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.

2024-04-03 | GSE217373 | GEO

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.

2019-06-21 | GSE131775 | GEO

Ptch1/Shh signaling control cochlear marginal cell differentiation and stria vascularis formation

Project description:Ptch1/Shh signaling control cochlear marginal cell differentiation and stria vascularis formation

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

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

| PRJNA544803 | ENA