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High-resolution transcriptional analysis reveals stepwise fate conversion of supporting cells to hair cells in the chicken auditory epithelium

ABSTRACT: High-resolution transcriptional analysis reveals stepwise fate conversion of supporting cells to hair cells in the chicken auditory epithelium

PROVIDER: PRJNA862478 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20654200_1.fastq.gz	Fastqsanger.gz
	SRR20654200_2.fastq.gz	Fastqsanger.gz
	SRR20654300_1.fastq.gz	Fastqsanger.gz
	SRR20654300_2.fastq.gz	Fastqsanger.gz
	SRR20654400_1.fastq.gz	Fastqsanger.gz

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High-resolution transcriptional analysis reveals stepwise fate conversion of supporting cells to hair cells in the chicken auditory epithelium

Project description:In contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor beta receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae.

2023-01-10 | GSE209791 | GEO

Ignition of supporting cell activation for hair cell regeneration in the avian auditory epithelium: an explant culture model

Project description:Sensorineural hearing loss is included in the most common disabilities, and often caused by loss of sensory hair cells in the cochlea. Hair cell regeneration has long been a main target for developing novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration occurs in very limited situations, while auditory epithelia of non-mammalians retain the capacity for hair cell regeneration. In the avian basilar papilla, an auditory sensory epithelium, supporting cells, which are sources for regenerated hair cells, are usually quiescent, while hair cell loss induces both direct transdifferentiation of supporting cells and mitotic division of supporting cells. In the present study, we aimed to establish an explant culture model for hair cell regeneration in chick basilar papillae, and validated usefulness of our model to investigate the initial phase of hair cell regeneration. Histological assessments demonstrated that hair cell regeneration via direct transdifferentiation of supporting cells occurred in our model. Labeling assay using 5-ethynyl-2'-deoxyuridine (EdU) revealed the occurrence of mitotic division of supporting cells in the specific location in basilar papillae, while no EdU labeling was identified in newly generated HCs. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, which is consistent with previous findings. In addition, unbiased analyses of RNA sequencing data indicated novel genes and signaling pathways that could be related to the ignition of supporting cell activation in chick basilar papillae. These results indicate the advantages of our model using explant cultures of chick basilar papillae for exploring molecular mechanisms for hair cell regeneration. Further studies such as single-cell RNA sequencing will allow us to capture the spatiotemporal information by using our explant culture model.

2020-10-23 | GSE154375 | GEO

Mapping the regulatory landscape of auditory hair cells from single cell multi-omics data

Project description:Auditory hair cells transduce sound to the brain and in mammals these cells reside together with supporting cells in the sensory epithelium of the cochlea, called the organ of Corti. To establish the organ’s delicate function during development and differentiation, spatiotemporal gene expression is strictly controlled by chromatin accessibility and cell type specific transcription factors, jointly representing the regulatory landscape. Bulk-sequencing technology and cellular heterogeneity obscured investigations on the interplay between transcription factors and chromatin accessibility in inner ear development. To study the formation of the regulatory landscape in hair cells, we collected single-cell chromatin accessibility profiles accompanied by single-cell RNA data from genetically labeled murine hair cells and supporting cells after birth.

2021-03-11 | GSE157398 | GEO

Stepwise fate conversion of supporting cells to sensory hair cells in the chick auditory epithelium.

Project description:In contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor β receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae.

| S-EPMC9932131 | biostudies-literature

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

Ignition of supporting cell activation for hair cell regeneration in the avian auditory epithelium: an explant culture model

Project description:Ignition of supporting cell activation for hair cell regeneration in the avian auditory epithelium: an explant culture model

| PRJNA646062 | ENA

Gene Expression from hair cells and supporting cells in chick utricle

2016-05-17 | GSE81461 | GEO

Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells

Project description:Mammalian cochlear outer hair cells (OHCs) are essential for hearing. Severe hearing impairment follows OHC degeneration. Previous attempts at regenerating new OHCs from cochlear supporting cells (SCs) have been unsuccessful, notably lacking expression of the key OHC motor protein, Prestin. Thus, regeneration of Prestin+ OHCs represented a barrier to restoring auditory function in vivo. Here, we reported the successful in vivo conversion of adult mouse cochlear SCs into Prestin+ OHC-like cells through the concurrent induction of two key transcriptional factors known to be necessary for OHC development: Atoh1 and Ikzf2. Single cell RNA sequencing reveals the upregulation of 729 OHC genes and downregulation of 331 SC genes in OHC-like cells. The resulting differentiation status of these OHC-like cells was much more advanced than previously achieved. This study thus established an efficient approach to induce the regeneration of Prestin+ OHCs, paving the way for in vivo cochlear repair via SC transdifferentiation.

2021-09-03 | GSE161156 | GEO

Identification of intermediate transcriptome states and synergistic effects of Isl1 in Atoh1-mediated cochlear hair cell conversion

Project description:Ectopic expression of Atoh1 in non-sensory supporting cells (SCs) in mouse cochleae induces their conversion to hair cells (HCs) in vivo. cHCs in multiple intermediate states of the conversion process that most closely resembled neonatal differentiating HCs, but differed from the progenitors. We further identified 52 transcription factors that are differentially expressed in cHCs, SCs, and mature HCs and confirmed that Isl1 synergistically enhanced the efficiency of Atoh1-mediated HC conversion in cochlear explants. Our results demonstrate that direct HC conversion from SCs in vivo follows a different path from normal development and requires multiple factors for maximum efficiency and completion.

2018-07-23 | GSE85983 | GEO

Transcription profiling of rat hair and supporting cells from the cristae ampullaris in the inner ear

Project description:Using laser capture microdisection, the more superficial layer of the cristae ampullaris sensory epithelium encompassing types I and II hair cells, and the supporting cell cytoplasm interspersed between them was captured in the first pass, and the underlying supporting cell bodies resting on the basal lamina were captured in a second pass. Individual hair cells were identified under light microscopy at 200X magnification by their stereociliary tuft and the calyceal nerve ending surrounding them and the presence of their nucleus in the outermost portion of the epithelia.

2008-05-01 | E-MEXP-1559 | biostudies-arrayexpress

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