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Transcriptomic and epigenetic analysis of neonatal supporting cells during Notch inhibition-induced transdifferentiation

ABSTRACT: Transcriptomic and epigenetic analysis of neonatal supporting cells during Notch inhibition-induced transdifferentiation

PROVIDER: PRJNA630760 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11714343_1.fastq.gz	Fastqsanger.gz
	SRR11714343_2.fastq.gz	Fastqsanger.gz
	SRR11714344_1.fastq.gz	Fastqsanger.gz
	SRR11714344_2.fastq.gz	Fastqsanger.gz
	SRR11714345_1.fastq.gz	Fastqsanger.gz

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Transcriptomic and epigenetic analysis of neonatal supporting cells during Notch inhibition-induced transdifferentiation

Project description:Latent regeneration potential has been found in neonatal supporting cells in the organ of Corti in mouse. Upon Notch inhibition by DAPT, postnatal day 1 (P1) supporting cells transdifferentiate into hair cells. To profile the transcriptomic and epigenetic changes in supporting cells during transdifferentiation, we FACS purified supporting cells from DAPT treated cochleae for RNAseq, ATACseq and H3K27ac CUT&RUN. We found that hair cell genes were up-regulated in supporting cells after DAPT treatment and that hair cell gene induction was accompanied by epigentic activation of hair cell gene cis-regulatory elements through chromatin accessibility increase and H3K27ac accumulation, suggesting the regulatory roles of epigenetic activation of hair cell gene elements for hair cell gene expression induction.

2021-07-09 | GSE150002 | GEO

Transcriptomic analysis of neonatal supporting cells after histone modification perturbations

Project description:At neonatal stage, sensory hair cell gene promoters and enhancers are primed by H3K4me3/me1 in neighboring supporting cells, but silenced by deacetylation and H3K27 tri-methylation. To test whether this primed-but-silenced epigenetic status leads to the repressed expression of hair cell genes in supporting cells, we FACS-purified Lfng-GFP+ supporting cells from cultured postnatal day 1 (P1) ochlear organs 48 hours after TSA (HDAC inhibitor) or GSK-343 (EZH2 inhibitor) for transcritomic analysis by RNAseq. We found that hair cell genes could be induced by either blocking of histone deacetylation or inhibition of H3K27 trimethylation, suggesting histone deacetylation and H3K27 trimethylation are required to repress hair cell gene expression in supporting cells at neonatal stage when a latent transdifferentiation potential still exists in supporting cells.

2021-07-09 | GSE150001 | GEO

RNA-seq analysis of neonatal mouse cochlear supporting cells [Treated AK]

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

RNA-seq analysis of neonatal mouse cochlear supporting cells [Treated AK]

2016-07-01 | GSE83340 | GEO

Notch Signaling Plays an Instructive Role in Supporting Cell Development and is Critical for Supporting Cell Survival

Project description:The sensory epithelium of the cochlea is a specialized structure responsible for the perception of sound. While much is understood about the development of the mechanosensory hair cells found within this epithelium, little is known about the development of the glial-like supporting cells. Here, we provide evidence that in addition to its well-characterized inhibitory function, canonical Notch signaling plays a positive, instructive role in the differentiation of supporting cells. Using γ-secretase inhibitor DAPT to acutely block canonical Notch signaling, we identified a cohort of Notch-regulated supporting cell-specific genes, with diverse functions in cell signaling, cell differentiation, neuronal innervation and synaptogenesis.

2016-02-01 | GSE67085 | GEO

Epigenetic analysis of perinatal maturation of supporting cells in the organ of Corti

Project description:Sensory hair cells cannot be regenerated through transdifferentiation of neighboring supporting cells in the organ of Corti in mature mammalian animals, but limited regeneration capacity exists in supporting cells at neonatal stage in mouse and this transdifferentiation potential is rapidly lost during the first week of postnatal maturtion. We hypothesized that epigenetic decommissioning of hair cell gene enhancers in supporting cells during postnatal maturation leads the permanent silencing of hair cell genes and the loss of transdifferentiation potential. To test this hypothesis, we FACS purified hair cells and supporting cells from cochleae at different developmental stages for transcritomic analysis (RNAseq), chromatin accessibility assay (ATACseq) and histone modification profiling (ChIPseq or CUT&RUN). We first defined hair cell genes and predicted their potential active enhancers. We found that hair cell gene promoters and enhancers were kept in a primed-but-silenced status (H3K4me1/3+, low H3K27ac but high H3K27me3) in supporting cells at neonatal stage. During postnatal maturation, hair cell gene enhancers are decommissioned through H3K4me1 removal, leading to the permanent silencing of hair cells genes. We also found that hair cell gene enhancer decommissioning process correlated with the base-to-apex wave of transdifferentiation potential loss. In addition, hair cell gene enhancer commissioning status is preserved in mature utricular supporting cells, which can regenerate hair cells through transdifferentiation even at adult stage. Those data together suggest that decommissioning of hair cell gene enhancers in supporting cells during postnatal maturation is the epigenetic mechanism underlying the loss of regeneration capacity in the organ of Corti.

2021-07-09 | GSE150000 | GEO

RNA-seq analysis of neonatal mouse cochlear supporting cells [NonTreated_JM]

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

Expression data from human neonatal melanocytes and Notch transformed human neonatal melanocytes

Project description:Notch1 Activation Confers Transforming Properties to Primary Human Melanocytes and Promotes Human Melanoma Progression We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Human neonatal melanocytes and Notch transformed human neonatal melanocytes were selected for RNA extraction and hybridization on Illumina gene expression array chip. Expression intensities were calculated and normalized for each gene probed on the array for all hybridizations using illumina Beadstudio#3 software. Microarray analyses were subsequently performed in GeneSpring to aid in the identification of genes differentially-expressed between Notch-infected and control melanocytes that may be responsible for the phenotypic changes described in the NIC-infected cells.

2010-06-25 | E-GEOD-15040 | biostudies-arrayexpress

Epigenetic and Transcriptional Regulation of Supporting Cell to Hair Cell Transdifferentiation

Project description:Epigenetic and Transcriptional Regulation of Supporting Cell to Hair Cell Transdifferentiation

| PRJNA548558 | ENA

RNA-seq analysis of neonatal mouse cochlear supporting cells

Project description:RNA-seq analysis of neonatal mouse cochlear supporting cells

| PRJNA325664 | ENA