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Precise genetic control of ATOH1 enhances maturation of regenerated hair cells in mouse utricle

ABSTRACT: Precise genetic control of ATOH1 enhances maturation of regenerated hair cells in mouse utricle

PROVIDER: PRJNA1055553 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR25638704.fastq.gz	Fastqsanger.gz
	SRR25638705.fastq.gz	Fastqsanger.gz
	SRR25638706.fastq.gz	Fastqsanger.gz
	SRR25638707.fastq.gz	Fastqsanger.gz

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Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1

Project description:The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by reprogramming of supporting cells with the hair cell transcription factor Atoh1. We used RNA-seq and ATAC-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. We show that the improved regenerative response of the utricle correlates with a more accessible chromatin structure in utricle supporting cells compared to their cochlear counterparts. We also provide evidence that Atoh1 transduction of supporting cells is able to promote increased transcriptional accessibility of some hair cell genes. Our study offers a possible explanation for regenerative differences between sensory organs of the inner ear, but shows that additional factors to Atoh1 may be required for optimal reprogramming of hair cell fate.

2019-04-30 | GSE121610 | GEO

Characterization of the transcriptomes of Atoh1-induced hair cells in the mouse cochlea

Project description:Mammalian cochlea hair cells can be regenerated from the adjacent supporting cells in many ways, however, the newly hair cells are immature and without hearing function almost. The expression of Atoh1 is an important maker of the appearance of newly hair cells, many approaches of inner ear hair cells’ regeneration are concerned with the transcription factor Atoh1. However, most new HCs are immature HCs, and they do not have the function of mature HCs and eventually die a few weeks after regeneration. Thus promoting the maturation and survival of new HCs is the primary focus of HC regeneration field. We used RNA-Seq analysis to compare the differences between the transcriptomes of Atoh1 overexpression-induced new HCs and the original HCs, and to define the factors that might help to promote the maturation and survival of new HCs.

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Gene Expression from hair cells and supporting cells in chick utricle

Project description:In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, birds can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. We used microarrays to identify novel genes related to the regeneration in the chicken utricle. Supporting cell and hair cell populations of chicken utricle obtained by laser capture microdissection, following to do RNA extraction and hybridization on Affymetrix microarrays.

2016-05-17 | E-GEOD-81461 | biostudies-arrayexpress

Rat utricle hair bundles and whole utricles—LTQ

Project description:Purified utricle hair bundles and utricular epithelium from P3-P7 rat inner ears were analyzed by LC-MS/MS to determine the abundant and enriched proteins of the hair bundle. This dataset used a Thermo LTQ mass spectrometer for protein detection.

2015-11-17 | PXD002416 | Pride

Precise genetic control of ATOH1 enhances maturation of regenerated hair cells in mouse utricle

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-09-24 | GSE251854 | GEO

Mouse utricle hair bundles and whole utricles—Velos

Project description:Purified utricle hair bundles and utricular epithelium from P21-P25 mouse inner ears were analyzed by LC-MS/MS to determine the abundant and enriched proteins of the hair bundle. This dataset used a Thermo LTQ Velos mass spectrometer for protein detection.

2015-11-17 | PXD002415 | Pride

In Vivo and Ex Vivo Utricles treated with ATOH1 under different promoters

Project description:Vestibular hair cells are mechanoreceptors critical for detecting head position and motion. In mammals, hair cell loss causes vestibular dysfunction as spontaneous regeneration is nearly absent. Constitutive expression of exogenous ATOH1, a hair cell transcription factor, increases regeneration of hair cells, but these cells fail to mature. With the aim of developing an optimized AAV-based ATOH1 gene therapy, we used single-cell RNA-Seq and explored the impact of defined promoters on ATOH1 transgene expression level, timing, effects in distinct cell types, and the maturity of regenerated vestibular hair cells ex vivo and in vivo.

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Gallus gallus utricle striola vs. extra-striola

Project description:The inner ear utilizes sensory hair cells as mechano-electric transducers for sensing sound and balance. In mammals, these hair cells lack the capacity for regeneration. Unlike mammals, hair cells from non-mammalian vertebrates, such as birds, can be regenerated throughout the life of the organism making them a useful model for studying inner ear genetics pathways. The zinc finger transcription factor GATA3 is required for inner ear development and mutations cause sensory neural deafness in humans. In the avian cochlea GATA3 is expressed throughout the sensory epithelia; however, expression is limited to the striola of the utricle. The striola corresponds to an abrupt change in morphologically distinct hair cell types and a 180° shift in hair cell orientation. We used 3 complimentary approaches to identify potential downstream targets of GATA3 in the avian utricle. Specifically we used microarray expression profiling of GATA3 knockdown by siRNA and GATA3 over-expression treatments as well as direct comparisons of GATA3 expressing cells from the striola and non GATA3 expressing cells from the extra-striola. To identify genes that are co-expressed with GATA3 at the striola reversal zone, we compared gene expression in cells micro-dissected from the sensory epithelia of the chick utricle striola to cells from the surrounding extra-striola. There are 2 biological samples and experiments include technical replicates as well as dye-switches for a total of 8 microarrays.

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GATA3 siRNA in utricle sensory epithelia

Project description:The inner ear utilizes sensory hair cells as mechano-electric transducers for sensing sound and balance. In mammals, these hair cells lack the capacity for regeneration. Unlike mammals, hair cells from non-mammalian vertebrates, such as birds, can be regenerated throughout the life of the organism making them a useful model for studying inner ear genetics pathways. The zinc finger transcription factor GATA3 is required for inner ear development and mutations cause sensory neural deafness in humans. In the avian cochlea GATA3 is expressed throughout the sensory epithelia; however, expression is limited to the striola of the utricle. The striola corresponds to an abrupt change in morphologically distinct hair cell types and a 180Â° shift in hair cell orientation. We used 3 complimentary approaches to identify potential downstream targets of GATA3 in the avian utricle. Specifically we used microarray expression profiling of GATA3 knockdown by siRNA and GATA3 over-expression treatments as well as direct comparisons of GATA3 expressing cells from the striola and non GATA3 expressing cells from the extra-striola. Whole utricle specimens were treated with streptomycin for 24 hrs, rinsed and allowed to recover for an additional 24 hrs. Whole utricles were transfected with either GATA3 or GFP 21mer synthetic siRNAs for an additional 48 hrs and pure sensory epithelia were isolated. There are 2 biological samples and experiments include technical replicates as well as dye-switches for a total of 8 microarrays.

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RNA-seq analysis of hair cell regeneration in the mammalian vestibular system and its potentiation by Atoh1

Project description:We used RNA-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction.

2019-05-07 | GSE122732 | GEO

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