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Pseudo-temporal analysis of Single-cell RNA sequencing reveals trans-differentiation potential of Greater Epithelial Ridge cells into hair cells during postnatal development of cochlea in Rats

ABSTRACT: Pseudo-temporal analysis of Single-cell RNA sequencing reveals trans-differentiation potential of Greater Epithelial Ridge cells into hair cells during postnatal development of cochlea in Rats

PROVIDER: PRJNA801859 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17818682_1.fastq.gz	Fastqsanger.gz
	SRR17818682_2.fastq.gz	Fastqsanger.gz
	SRR17818683_1.fastq.gz	Fastqsanger.gz
	SRR17818683_2.fastq.gz	Fastqsanger.gz
	SRR17818684_1.fastq.gz	Fastqsanger.gz

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Pseudo-temporal analysis of Single-cell RNA sequencing reveals trans-differentiation potential of Greater Epithelial Ridge cells into hair cells during postnatal development of cochlea in Rats

Project description:The hair cells of the cochlea play a decisive role in the process of hearing damage and recovery, yet knowledge of their regeneration process is still limited. Greater epithelial ridge (GER) cells, a type of cell present during cochlear development that has the characteristics of a precursor sensory cell, disappear at the time of maturation of hearing development. Its development and evolution remain mysterious for many years. Here, we performed single-cell RNA sequencing to profile the gene expression landscapes of rats' cochlear duct from P1, P7, and P14 and identified eight major subtypes of GER cells. Furthermore, single-cell trajectory analysis for GER cells and hair cells indicated that among the different subtypes of GER, four subtypes had transient cell proliferation after birth and could transdifferentiate into inner and outer hair cells, and two of them mainly transdifferentiated into inner hair cells. The other two subtypes eventually transdifferentiate into outer hair cells. Our study lays the groundwork for elucidating the mechanisms of the key regulatory genes and signaling pathways in the trans-differentiation of GER cell subtypes into hair cells and provides potential clues to understand hair cell regeneration.

2022-01-29 | GSE195702 | GEO

Single-cell RNA sequencing analysis reveals Greater Epithelial Ridge cells degeneration during postnatal development of cochlea in Rats

Project description:Greater epithelial ridge cells, a transient neonatal cell group in the cochlear duct, which plays a crucial role in the functional maturation of hair cell, structural development of tectorial membrane, and refinement of audio localization before hearing. Greater epithelial ridge cells are methodologically homogeneous, while whether different cell subtypes are existence in this intriguing region and the degeneration mechanism during postnatal cochlear development are poorly understood. In the present study, single-cell RNA sequencing was performed on the cochlear duct of postnatal rats at day 1 (P1) and day 7 (P7) to identify subsets of greater epithelial ridge cell and progression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to examine genes enriched biological processes in these clusters. We identified a total of 26 clusters at P1 and P7 rats and found that the cell number of five cell clusters decreased significantly, while four clusters had similar gene expression patterns and biological properties. The genes of these four cell populations were mainly enriched in Ribosome and P13K-Akt signal pathway. Among them, Rps16, Rpsa, Col4a2, Col6a2, Ctsk, and Jun are particularly interesting as their expression might contribute to the greater epithelial ridge cells degeneration. In conclusion, our study provides an important reference resource of greater epithelial ridge cells landscape and mechanism insights for further understanding greater epithelial ridge cells degeneration during postnatal rat cochlear development

2021-09-02 | GSE170810 | GEO

Single-cell RNA sequencing analysis reveals Greater Epithelial Ridge cells degeneration during postnatal development of cochlea in Rats

Project description:Single-cell RNA sequencing analysis reveals Greater Epithelial Ridge cells degeneration during postnatal development of cochlea in Rats

| PRJNA717971 | ENA

Greater epithelial ridge cells are the principal organoid-forming progenitors of the mouse cochlea.

Project description:In mammals, hearing loss is irreversible due to the lack of regenerative potential of non-sensory cochlear cells. Neonatal cochlear cells, however, can grow into organoids that harbor sensory epithelial cells, including hair cells and supporting cells. Here, we purify different cochlear cell types from neonatal mice, validate the composition of the different groups with single-cell RNA sequencing (RNA-seq), and assess the various groups' potential to grow into inner ear organoids. We find that the greater epithelial ridge (GER), a transient cell population that disappears during post-natal cochlear maturation, harbors the most potent organoid-forming cells. We identified three distinct GER cell groups that correlate with a specific spatial distribution of marker genes. Organoid formation was synergistically enhanced when the cells were cultured at increasing density. This effect is not due to diffusible signals but requires direct cell-to-cell contact. Our findings improve the development of cell-based assays to study culture-generated inner ear cell types.

| S-EPMC7847202 | biostudies-literature

Single-Cell RNA Sequencing Analysis Reveals Greater Epithelial Ridge Cells Degeneration During Postnatal Development of Cochlea in Rats.

| S-EPMC8446670 | biostudies-literature

Proteome Comparison of Different-Aged Cochlea

Project description:Our work describes the application of mass spectrometry-based label-free quantitative proteomics for the identification of differentially expressed proteins between different-aged cochlea. We report proteins exclusively present as well as up- and downregulated in the cochlear sensory epithelium at significant developmental stages. Additionally, we report proteins exclusively present on P3 that were recently identified in the cochlea for the first time. We use bioinformatics to provide insight on biological functions and potential primary and secondary partners of the differentially expressed proteins. This study provides the first differentially expressed proteome in the mammalian cochlea at significant developmental stages; before hearing, during the onset of hearing, and when hearing is fully developed. We believe that these results will provide insights into the function of proteins that change during development and identify potential protein biomarkers related to hearing impairments.

2018-08-29 | PXD001973 | Pride

Expression of Atoh1, Gfi1, and Pou4f3 in the mature cochlea reprograms non-sensory cells into hair cells

Project description:Mechanosensory hair cells of the mature mammalian organ of Corti do not regenerate, and loss of hair cells leads to permanent hearing loss. Although non-mammalian vertebrates are able to regenerate hair cells by the division and transdifferentiation of adjacent supporting cells, many humans with severe hearing loss completely lack hair cells and supporting cells, with the organ of Corti being replaced by a flat epithelium of non-sensory cells To determine if mature non-sensory cells can produce hair cells in vivo, we reprogrammed non-sensory cells of the mature cochlea with three hair cell transcription factors, Gfi1, Atoh1, and Pou4f3. We were able to generate significant numbers of hair cell-like cells in the non-sensory inner and outer sulci of the cochlea after 2 weeks of reprogramming. New hair cells continued to be added to the non-sensory regions of the cochlea over the next seven weeks, and expressed hair cell proteins such as Myosin VIIa, parvalbumin, and prestin and formed stereociliary hair bundles. We confirmed the identity of these cells by high depth single cell RNA-seq. Significantly, cells adjacent to converted hair cells expressed markers of supporting cells, suggesting that transcription factor reprogramming of non-sensory tissue in the adult animal can generate mosaics of sensory cells similar to those seen in the organ of Corti. Generating such sensory mosaics by reprogramming may represent a potential strategy for hearing restoration in humans.

2024-01-03 | GSE224627 | GEO

Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea.

Project description:Foxg1 is one of the forkhead box genes that are involved in morphogenesis, cell fate determination, and proliferation, and Foxg1 was previously reported to be required for morphogenesis of the mammalian inner ear. However, Foxg1 knock-out mice die at birth, and thus the role of Foxg1 in regulating hair cell (HC) regeneration after birth remains unclear. Here we used Sox2CreER/+ Foxg1loxp/loxp mice and Lgr5-EGFPCreER/+ Foxg1loxp/loxp mice to conditionally knock down Foxg1 specifically in Sox2+ SCs and Lgr5+ progenitors, respectively, in neonatal mice. We found that Foxg1 conditional knockdown (cKD) in Sox2+ SCs and Lgr5+ progenitors at postnatal day (P)1 both led to large numbers of extra HCs, especially extra inner HCs (IHCs) at P7, and these extra IHCs with normal hair bundles and synapses could survive at least to P30. The EdU assay failed to detect any EdU+ SCs, while the SC number was significantly decreased in Foxg1 cKD mice, and lineage tracing data showed that much more tdTomato+ HCs originated from Sox2+ SCs in Foxg1 cKD mice compared to the control mice. Moreover, the sphere-forming assay showed that Foxg1 cKD in Lgr5+ progenitors did not significantly change their sphere-forming ability. All these results suggest that Foxg1 cKD promotes HC regeneration and leads to large numbers of extra HCs probably by inducing direct trans-differentiation of SCs and progenitors to HCs. Real-time qPCR showed that cell cycle and Notch signaling pathways were significantly down-regulated in Foxg1 cKD mice cochlear SCs. Together, this study provides new evidence for the role of Foxg1 in regulating HC regeneration from SCs and progenitors in the neonatal mouse cochlea.

| S-EPMC7113235 | biostudies-literature

Pseudo-nitzschia multistriata

Project description:Pseudo-Nitzschia multistriata Project

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Pseudo-nitzschia multistriata

Project description:Pseudo-nitzschia multistriata overview

| PRJNA84105 | ENA