Ontology highlight
ABSTRACT:
PROVIDER: PRJNA900283 | ENA |
REPOSITORIES: ENA
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Project description:Strategies to overcome irreversible cochlear hair cell (HC) damage and loss are of vital importance to develop a treatment for hearing loss. HC regeneration in adult cochlea relies on a two-phase process: 1) Reprogramming mature cochlear (SCs) to regain the properties of their younger selves; 2) Activating Atoh1, a gene responsible for HC fate-determining, in the reprogrammed adult SCs for HC regeneration. We have shown that, by transient co-activation of Myc and NICD (Notch1 intracellular domain), the adult mouse cochlea can be successfully reprogrammed to a relatively younger stage and regain progenitor capacity, with the regeneration of HCs following Atoh1 overexpression in vitro and in vivo. To identify molecules to reprogram mature cochlear SCs and HC regeneration, we utilized single-cell RNA sequencing and uncovered the pathways and their target genes underlying MYC/NICD-mediated reprogramming. We used an in-house adult cochlea explant culture system and carried out single-cell RNA sequencing to examine the gene expression profiles of cochlear explants from a transgenic mouse model, rtTa/tet-Myc/-tet-NICD, in response to Dox-induced MYC/NICD co-activation. We compared gene expression profiles between Atoh1 activation vs. MYC/NICD/Atoh1 co-activation.
2023-06-01 | GSE218325 | GEO
Project description:Strategies to overcome irreversible cochlear hair cell (HC) damage and loss are of vital importance to develop a treatment for hearing loss. HC regeneration in adult cochlea relies on a two-phase process: 1) Reprogramming mature cochlear (SCs) to regain the properties of their younger selves; 2) Activating Atoh1, a gene responsible for HC fate-determining, in the reprogrammed adult SCs for HC regeneration. We have shown that, by transient co-activation of Myc and NICD (Notch1 intracellular domain), the adult mouse cochlea can be successfully reprogrammed to a relatively younger stage and regain progenitor capacity, with the regeneration of HCs following Atoh1 overexpression in vitro and in vivo. To identify molecules to reprogram mature cochlear SCs, we utilized single-cell RNA sequencing and uncovered the pathways and their target genes underlying MYC/NICD-mediated reprogramming. We used an in-house adult cochlea explant culture system and carried out single-cell RNA sequencing to examine the gene expression profiles of cochlear explants from a transgenic mouse model, rtTa/tet-Myc/-tet-NICD, in response to Dox-induced MYC/NICD co-activation. We have shown that a 4-day treatment by Dox in cultured adult rtTa/tetMyc/-tet-NICD cochleae was sufficient to reprogram adult SCs for HC regeneration.
2022-06-03 | GSE205187 | GEO
Project description:Strategies to overcome irreversible cochlear hair cell (HC) damage and loss are of vital importance to develop a treatment for hearing loss. HC regeneration in adult cochlea relies on a two-phase process: 1) Reprogramming mature cochlear (SCs) to regain the properties of their younger selves; 2) Activating Atoh1, a gene responsible for HC fate-determining, in the reprogrammed adult SCs for HC regeneration. We have shown that, by transient co-activation of Myc and NICD (Notch1 intracellular domain), the adult mouse cochlea can be successfully reprogrammed to a relatively younger stage and regain progenitor capacity, with the regeneration of HCs following Atoh1 overexpression in vitro and in vivo. We identified a combination (the cocktail) of drug-like molecules composing of small molecules and siRNAs to activate the pathways of Myc, Notch1, Wnt and cAMP. To identify molecules to reprogram mature cochlear SCs and HC regeneration, we utilized single-cell RNA sequencing and uncovered the pathways and their target genes underlying chemical-mediated reprogramming. We used an in-house adult cochlea explant culture system and carried out single-cell RNA sequencing to examine the gene expression profiles of cochlear explants, in response to chemical-induced reprogramming. We compared gene expression profiles between Vehicle/ad.Atoh1 activation vs. Cocktail (chemical reprogramming)/ad.Atoh1 activation.
2023-06-01 | GSE218324 | GEO
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear hair cells. Hair cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which the endogenous Atoh1 gene was fused with GFP Two replicates of GFP+ hair cells were compared with all other cochlear cell types that were GFP-
2015-03-01 | E-GEOD-65633 | biostudies-arrayexpress
Project description:Single cell gene expression profile of adult cochlear explants over the course of hair cell regeneration stimulated by chemical reprogramming [CocktailVehicleAtoh1]
| PRJNA903159 | ENA
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
Project description:We purified seven different cell populations and performed RNA sequencing to profile transcriptional similarities and differences between them. The seven cell types were 1) Atoh1-GFP positive cochlear hair cells from the organ of Corti of postnatal day one mice, 2) Atoh1-GFP negative cells from the organ of Corti of postnatal day one mice, 3) Atoh1-GFP positive induced hair cells generated by overexpression of Six1, Atoh1, Pou4f3, and Gfi1, 4) dsRed transduced control mouse embryonic fibroblasts, 5) Atoh1-GFP positive Merkel cells from postnatal day 1 mice, 6) Atoh1-GFP positive Cerebellar granule precursor cells from postnatal day 1 mice, and 7) Atoh1-GFP positive Gut secretory cells from postnatal day one mice.
2020-05-28 | GSE149259 | GEO
Project description:We purified seven different cell populations and performed RNA sequencing to profile transcriptional similarities and differences between them. The seven cell types were 1) Atoh1-GFP positive cochlear hair cells from the organ of Corti of postnatal day one mice, 2) Atoh1-GFP negative cells from the organ of Corti of postnatal day one mice, 3) Atoh1-GFP positive induced hair cells generated by overexpression of Six1, Atoh1, Pou4f3, and Gfi1, 4) dsRed transduced control mouse embryonic fibroblasts, 5) Atoh1-GFP positive Merkel cells from postnatal day 1 mice, 6) Atoh1-GFP positive Cerebellar granule precursor cells from postnatal day 1 mice, and 7) Atoh1-GFP positive Gut secretory cells from postnatal day one mice.
2020-05-28 | GSE149258 | GEO
Project description:We purified seven different cell populations and performed RNA sequencing to profile transcriptional similarities and differences between them. The seven cell types were 1) Atoh1-GFP positive cochlear hair cells from the organ of Corti of postnatal day one mice, 2) Atoh1-GFP negative cells from the organ of Corti of postnatal day one mice, 3) Atoh1-GFP positive induced hair cells generated by overexpression of Six1, Atoh1, Pou4f3, and Gfi1, 4) dsRed transduced control mouse embryonic fibroblasts, 5) Atoh1-GFP positive Merkel cells from postnatal day 1 mice, 6) Atoh1-GFP positive Cerebellar granule precursor cells from postnatal day 1 mice, and 7) Atoh1-GFP positive Gut secretory cells from postnatal day one mice.
2020-05-28 | GSE149257 | GEO
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