Similar Datasets
Project description:We report RNA-Seq analysis of the transcriptome of retinas and RPE/choroids from Abca4 knockout, Abca4 L541P;A1038V knockin and control wild type mice in order to better understand changes in gene regulation that could lead to retinal pathology in mice with ABCA4 deficiency/defect. Retinal and RPE/choroidal mRNA profiles of 30-day-old wild type (WT), Abca4-/- and Abca4L541P;A1038V/L541P;A1038V mice were generated by RNA-Seq, using Illumina Hiseq 2500
2015-04-07 | E-GEOD-63772 | biostudies-arrayexpress
Project description:We report RNA-Seq analysis of the transcriptome of retinas and RPE/choroids from Abca4 knockout, Abca4 L541P;A1038V knockin and control wild type mice in order to better understand changes in gene regulation that could lead to retinal pathology in mice with ABCA4 deficiency/defect.
2015-04-07 | GSE63772 | GEO
Project description:Stargardt retinopathy is an inherited form of macular degeneration caused by mutations in gene ABCA4 and characterized by the accumulation of lipid-rich deposits in the retinal pigment epithelium (RPE), RPE atrophy, and photoreceptor cell death. Inadequate mechanistic insights into pathophysiological changes occurring in Stargardt RPE have contributed to its lacking treatments. Here we show that ABCA4 knockout or Stargardt patient’s induced pluripotent stem cells-derived RPE (STGD1-iRPE) differentiate normally but display intracellular lipid and ceramide deposits reminiscent of the disease phenotype. STGD1-iRPE also shows defective photoreceptor outer segment (POS) processing and reduced cathepsin B activity, indicating higher lysosomal pH. Lipid deposits in STGD1-iRPE are reduced by increasing the activity of ABCA1, a lipid transporter, and ABCA4 ortholog. Overall, our work suggests that ABCA4 is involved in POS and lipid handling in RPE cells and provides guidance for ongoing gene therapy approaches to target both RPE and photoreceptor cells for an effective treatment.
2022-11-16 | GSE198362 | GEO
Project description:Vision depends on the functional interplay between the photoreceptor cells of the neural retina and the supporting cells of the underlying retinal pigment epithelium (RPE). Many genes involved in inherited retinal diseases (IRD) display highly specific spatiotemporal expression within these interconnected retinal components through the local recruitment of cis-regulatory elements (CREs) in 3D nuclear space. To understand the role of differential chromatin architecture in establishing tissue-specific expression patterns at IRD loci in the human neural retina and the RPE, we mapped genome-wide chromatin interactions by applying in situ Hi-C and H3K4me3 HiChIP to human adult post-mortem donor retinas. A comparative 3D genome analysis between neural retina and RPE revealed that almost 60% of known IRD genes were marked by differential cis-regulatory interactions or 3D genome structure. Furthermore, we zoomed in on tissue-specific chromatin interactions at the ABCA4 locus, which is implicated in the most common autosomal recessive IRD. We constructed high-resolution ABCA4 interaction profiles using UMI-4C, which, upon integration with bulk and single-cell epigenomic datasets and in vivo enhancer assays in zebrafish, revealed tissue-specific CREs for ABCA4. In summary, through extensive comparative 3D genome mapping, based on genome-wide (Hi-C), promoter-centric (HiChIP) and locus-specific (UMI-4C) assays of human neural retina and RPE, we have shown that gene regulation at key IRD loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes at retinal disease loci, but also delineate the search space for genomic variation underlying unsolved IRD.
2024-04-08 | GSE236021 | GEO
Project description:To determine the gene expression changes in the retina of Abca4-/-Rdh8-/- (dKO) mice, we collected retina samples from dKO animals under various experimental conditions, generated single-cell suspensions, and performed scRNA-Seq (10X Genomics).
2023-05-01 | GSE208760 | GEO
Project description:Precision medicine for ABCA4 disease: modifier alleles
| PRJNA717339 | ENA
Project description:Precision medicine for ABCA4 disease: modifier alleles
| PRJNA717338 | ENA
Project description:We wanted to transcriptomically compare single cells taken from the retinas of C57BL6/J mice, Abca4-/-Rdh8-/- (dKO) mutant mice, and Abca4PV/PVRdh8-/- (PVR) mutant mice before and at an early (24-hour post-bleach) timepoint post-bleaching, to see if the two Abca4 mutants displayed different transcriptomic shifts in response to intense light, which initiates retinal degeneration. Additionally, we wanted to determine if the two mutants had different transcriptional responses to the immunomodulatory drug maraviroc. The wild-type C57BL6/J mice were included as controls for each treatment condition. We profiled the three cohorts of mice under three separate treatment conditions: without light-induced degeneration, 24-hours post-bleaching with intense light and vehicle treatment, and 24-hours post-bleaching with intense light and maraviroc treatment. Single cell isolates were collected, fixed, barcoded, and sequenced using kits from Parse Biosciences.
2023-11-16 | GSE239347 | GEO
Project description:RNA-Seq of retina and RPE/choroid tissues from wild type, Abca4 knockout and Abca4 L541P A1038V knockin mice
| PRJNA269047 | ENA
Project description:Vision depends on the functional interplay between the photoreceptor cells of the neural retina and the supporting cells of the underlying retinal pigment epithelium (RPE). Many genes involved in inherited retinal diseases (IRD) display highly specific spatiotemporal expression within these interconnected retinal components through the local recruitment of cis-regulatory elements (CREs) in 3D nuclear space. To understand the role of differential chromatin architecture in establishing tissue-specific expression patterns at IRD loci in the human neural retina and the RPE, we mapped genome-wide chromatin interactions by applying in situ Hi-C and H3K4me3 HiChIP to human adult post-mortem donor retinas. A comparative 3D genome analysis between neural retina and RPE revealed that almost 60% of known IRD genes were marked by differential cis-regulatory interactions or 3D genome structure. Furthermore, we zoomed in on tissue-specific chromatin interactions at the ABCA4 locus, which is implicated in the most common autosomal recessive IRD. We constructed high-resolution ABCA4 interaction profiles using UMI-4C, which, upon integration with bulk and single-cell epigenomic datasets and in vivo enhancer assays in zebrafish, revealed tissue-specific CREs for ABCA4. In summary, through extensive comparative 3D genome mapping, based on genome-wide (Hi-C), promoter-centric (HiChIP) and locus-specific (UMI-4C) assays of human neural retina and RPE, we have shown that gene regulation at key IRD loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes at retinal disease loci, but also delineate the search space for genomic variation underlying unsolved IRD.
2024-04-08 | GSE235726 | GEO