Role of Jagged1 in cochlear supporting cell differentiation and maintenance
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ABSTRACT:
PROVIDER: PRJNA622802 | ENA |
REPOSITORIES: ENA
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Project description:Inner ear cochlear supporting cells (SCs) are highly specialized glia-like cells that structurally and functionally support neighboring mechano-sensory hair cells. Despite their importance for proper auditory function, little is known about the molecular mechanisms that control their development. In this study we investigated the function of the Notch ligand Jagged1 (Jag1) in cochlear SC differentiation and maintenance. To address the function of Jag1 in the differentiation of SCs, we conditionally deleted Jag1 in stage E14.5 SC precursors using the recently established Sox2-CreER/+ and Jag1 fx/fx mouse lines. Analysis of stage P0 Jag1 mutant and control animals revealed that Hensen cells, a highly specialized SC-subtype located at the lateral edge of the auditory sensory epithelium, failed to form in the absence of Jag1. Other SC-subtypes did form in the absence of Jag1, however, their morphology and cellular arrangement was abnormal and SC-subtype specific genes and genes associated with mitochondrial function and protein synthesis were significantly reduced, indicating global defects in SC differentiation and SC homeostasis.
2020-12-16 | GSE148009 | GEO
Project description:Hair cells (HCs) within the inner ear cochlea are highly specialized mechano-sensory cells that enable us to detect sound. In humans and other mammals, HC loss is permanent and a leading cause of deafness. Recent studies in newborn mice revealed that supporting cells (SCs) have the capacity to form cochlear HCs, and that inhibition of Notch signaling dramatically increases the otherwise low rate of SC-to-HC conversion. It has been proposed that in the absence of HCs, the SC-specific Notch ligand Jagged1 (JAG1) mediates the HC-repressive role of Notch signaling. Here we show that conditional deletion of Jag1 at postnatal day2 (P2) increases the rate of HC formation/regeneration in cochlear tissue and organoids. However, Jag1 deficiency also reduces the expression of key progenitor and metabolic genes and attenuates PI3K-Akt-mTOR signaling in cochlear SCs and Kölliker’s cells and we show that Notch1 and Notch2 are critical for mediating these pro-growth functions of Jag1. Conversely, we show that increasing JAG1/Notch signaling enhances the mitotic capacity of cochlear SCs/ Kölliker’s cells. Finally, we show that JAG1 expression declines in SCs as they undergo maturation, and that stimulation of JAG1 signaling boosts the ability of maturing cochlear SCs to form HCs in an mTOR-dependent manner.
2025-06-21 | GSE266157 | GEO
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 1 and postnatal day 6. mRNA profiles of supporting cells (GFP+) and all other cochlear cell types (GFP-), two replicates each, at P1 and P6 mice were generated by deep sequencing using Illumna TruSeq.
2016-07-01 | E-GEOD-83356 | biostudies-arrayexpress
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6 after inhibition of the Notch signaling pathway. Cochleas from postnatal day 0 and postnatal day 5 were cultured for 24 hours in the gamma secretase inhibitor DAPT or DMSO as a vehicle control. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 0+24 hours culture and postnatal day 5 + 24 hours culture. (corresponding to P1 and P6). mRNA profiles of P0 and P5 supporting cells (GFP+) and all other cochlear cell types (GFP-) treated with DAPT or DMSO, two replicates each, were generated by deep sequencing using Illumna TruSeq.
2016-07-01 | E-GEOD-83340 | biostudies-arrayexpress
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 1 and postnatal day 6.
2016-07-01 | GSE83356 | GEO
Project description:The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration
| PRJNA1106021 | ENA
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6 after inhibition of the Notch signaling pathway. Cochleas from postnatal day 0 and postnatal day 5 were cultured for 24 hours in the gamma secretase inhibitor DAPT or DMSO as a vehicle control. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 0+24 hours culture and postnatal day 5 + 24 hours culture. (corresponding to P1 and P6).
2016-07-01 | GSE83340 | GEO
Project description:RNA-seq analysis of neonatal mouse cochlear supporting cells
| PRJNA325664 | ENA
Project description:Reprogramming of cochlear supporting cells by MYC/NICD co-activation.
| PRJNA844057 | ENA
Project description:Characterizing adult cochlear supporting cell transcriptional diversity using scRNA-Seq Hearing loss is a significant disability that impacts 432 million people worldwide. A significant proportion of these individuals are dissatisfied with or do not have access to available treatment options which include hearing aids and cochlear implants. An alternative approach to restore hearing would be to regenerate lost cells, including hair cells in the adult cochlea. Such therapy would require restoration of the organ of Corti’s complex architecture, necessitating regeneration of both mature hair cells and supporting cells. We characterize the first single-cell adult cochlear supporting cell transcriptomes with the goals of: (1) demonstrating their transcriptional distinctiveness from perinatal cochlear supporting cells, (2) providing a metric for future attempts at regenerating mature cochlear supporting cells by identifying both cell type-specific and regional-specific expression, and (3) identify cell cycle gene expression present in adult supporting cells at the single cell level which may establish a basis for targeting cell cycle regulation pathways to force these cells out of quiescence.
2020-02-19 | GSE135703 | GEO