The function of Trim71 in supporting cell reprogramming and hair cell regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA865542 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20773619_1.fastq.gz | Fastqsanger.gz | |||
| SRR20773619_2.fastq.gz | Fastqsanger.gz | |||
| SRR20773620_1.fastq.gz | Fastqsanger.gz | |||
| SRR20773620_2.fastq.gz | Fastqsanger.gz | |||
| SRR20773621_1.fastq.gz | Fastqsanger.gz |
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Project description:Employing an organoid based assay, we show that lentiviral overexpression of human TRIM71 in stage P5 cochlear epithelial cells restores their capacity to proliferate and form hair cells. RNA-sequencing and cell-based assays reveal that similar to LIN28B, TRIM71 overexpression activates the expression of pro-growth genes and inhibits pro-differentiation genes resulting in the reprogramming of supporting cells into progenitor like cells.
2023-08-01 | GSE210383 | GEO
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
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
Project description:A major cause of human deafness and vestibular dysfunction is permanent loss of the mechanosensory hair cells of the inner ear. In non-mammalian vertebrates such as zebrafish, regeneration of missing hair cells can occur throughout life. While a comparative approach has the potential to reveal the basis of such differential regenerative ability, the degree to which the inner ears of fish and mammals share common hair and supporting cell types remains unresolved. Here we perform single-cell RNA sequencing of the zebrafish inner ear at embryonic through adult stages to catalog the diversity of hair and non-sensory supporting cells. We identify a putative progenitor population for hair and supporting cells, as well as distinct hair and supporting cell types in the maculae versus cristae. The hair and supporting cell types differ from those described for the lateral line, a distributed mechanosensory organ in zebrafish in which most studies of hair cell regeneration have been conducted. In the maculae, we identify two subtypes of hair cells that share gene expression with mammalian striolar or extrastriolar hair cells. In situ hybridization reveals that these hair cell subtypes occupy distinct spatial domains within the two major macular organs, the utricle and saccule, consistent with the reported distinct electrophysiological properties of hair cells within these domains. These findings suggest that primitive specialization of spatially distinct striolar and extrastriolar hair cells likely arose in the last common ancestor of fish and mammals. The similarities of inner ear cell type composition between fish and mammals also support using zebrafish as a relevant model for understanding inner ear-specific hair cell function and regeneration.
2023-01-04 | GSE211728 | GEO
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.
2016-05-17 | GSE81461 | GEO
Project description:Follistatin promotes LIN28B mediated supporting cell reprogramming and hair cell regeneration in the murine cochlea
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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
Project description:Latent transdifferentiation potential exists in supporting cells at neonatal stage in the organ of Corti in mouse, but this plasticity is lost rapidly during the first week of postnatal maturation, leading to the failure of sensory hair cell regeneration. To investigate the molecular mechanism underlying the loss of transdifferentiation potential, we compared epigenetic changes in E17.5, P1 and P6 supporting cells. In E17.5 and P1 supporting cells, hair cell gene enhancers are kept in a primed state (H3K4me1+ H3K27ac-) which can be readily activated during transdifferentiation induced by Notch blocking. As supporting cells mature, a substantial amount of hair cell gene enhancers are decommissioned by H3K4me1, leading to the loss of transdifferentiation potential. In contrast, hair cell gene enhancers retain their commissioned epigenetic status in mature utricular supporting cells, sustaining the transidifferentiation potential in utricular supporting cells in mature animals. Our findings reveal the epigenetic mechanisms underlying the failure of sensory hair cell regeneration in mammalian cochlea.
2021-07-09 | GSE150010 | GEO
Project description:Current global gene expression techniques allow the evaluation and comparison of the expression of thousands of genes in a single experiment, providing a tremendous amount of information. However, the data generated by these techniques are context-dependent, and minor differences in the individual biological samples, methodologies for RNA acquisition, amplification, hybridization protocol and gene chip preparation, as well as hardware and analysis software, lead to poor correlation between the results. In the inner ear the acquisition of RNA from individual cell populations remains a challenge due to the high density of the different cell types and the paucity of tissue. Consequently laser capture microdissection was used to selectively collect individual cells and regions of cells from cristae ampullares followed by extraction of total RNA and amplification to amounts sufficient for high throughput analysis. To demonstrate hair cell specific gene expression, myosin VIIA, calmodulin, and alpha9 nicotinic acetylcholine receptor subunit mRNAs were amplified using RT-PCR. To demonstrate supporting cell specific gene expression, cyclin-dependent kinase inhibitor p2kip1 mRNA was amplified using RT-PCR. Subsequent experiments with alpha9 RT-PCR demonstrated phenotypic differences between type I and type II hair cells, with expression only in type II hair cells. Using the laser capture microdissection technique, microarray expression profiling demonstrated 408 genes with more than a five-fold difference in expression between the hair cells and supporting cells, of these 15 were well annotated. There were 9 annotated genes with greater than a five-fold expression difference in the hair cells relative to the supporting cells, and 8 annotated genes with greater than a five-fold expression difference in the supporting cells relative to the hair cells. Keywords: hair cell specific gene expression, laser capture microdissection
2007-11-27 | GSE9684 | GEO
Project description:Purpose - To profile epigenetic changes in cochlear progenitor cells, hair cells, and supporting cells across postnatal development. Methods- Cochlear cell types were obtained from fluorescently labeled transgenic mice. E13.5 cochlear prosensory progenitor cells (E13.5_PG, p27Kip1-GFP+), P1 hair cells (P1_HC, Atoh1-GFP+), P1 supporting cells (P1_SC, Lfng-GFP+), and P6, P8, P21 supporting cells (P6_SC, P8_SC, P21_SC, Lfng-creER, NuTRAP lineage-traced) were FACS purified for epigenetic profiling using WGBS (DNA methylation), CUT&Tag (H3K4me1, H3K4me3, H3K27me3, CUTAC H3K4me2). DNA demethylation of hair cell-specific promoters was interrogated by comparing % mCpG profiles of transdifferentiating supporting cells (P1_SC_tdt_gfp, Lfng-creER/TdTomato+, Atoh1-GFP+) against non-transdifferentiating supporting cells (P1_SC_tdt, P6_SC_tdt, Lfng-creER/TdTomato+) purified via FACS. P1 and P8 wildtype cochleas were enzymatically dissociated and used directly for scMultiome simultaneous profiling of RNA and ATAC at the single cell level (P1_scMultiome, P8_scMultiome, 10x Genomics). For scMultiome of P70 wildtype (P70_wt_scMultiome, Lfng-CreERT2, NuTRAP) and P70 deafened (P70_deaf_scMultiome, Lfng-CreERT2, NuTRAP, Pou4f3DTR) supporting cells, mice received 100 mg/kg tamoxifen (Sigma-Aldrich T5648) at P21, 0.01 mg/kg Diptheria toxin (Sigma-Aldrich D0564) at P28, and allowed to mature to P70, at which point cochlear tissues were harvested, FACS purified for NuTRAP+ supporting cells, and inputted into a scMultiome reaction. Results- WGBS highlighted differentially methylated regions (DMR) across E13.5_PG, P1_HC, P1_SC, P6_SC, and P21_SC. Pre-established DMRs become hypermethylated in supporting cells between P1 and P21. This corresponds with increasing heterochromatin characteristics, such as loss of accessibility (CUTAC), loss of H3K4me1, and switch between H3K27me3-mediated repression to DNA methylation-mediated silencing. WGBS of P1_SC_tdt_gfp compared to P1_SC_tdt and P6_SC_tdt showed DNA demethylation of hair cell-specific DMRs, suggesting that DNA demethylation is required for transdifferentiation of supporting cells into hair cells. P1_scMultiome, P8_scMultiome, P70_wt_scMultiome, and P70_deaf_scMultiome revealed changes in chromatin accessibility associated with age, as well as from long-term deafening at the single cell level. scMultiome datasets also highlight cell type-specific enhancers active during different stages of postnatal development.
2023-02-07 | GSE224563 | GEO