Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-Seq of retina and RPE/choroid tissues from wild type, Abca4 knockout and Abca4 L541P;A1038V knockin mice

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Ning Zhang

PROVIDER: E-GEOD-63772 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Protein misfolding and the pathogenesis of ABCA4-associated retinal degenerations.

Zhang Ning N Tsybovsky Yaroslav Y Kolesnikov Alexander V AV Rozanowska Malgorzata M Swider Malgorzata M Schwartz Sharon B SB Stone Edwin M EM Palczewska Grazyna G Maeda Akiko A Kefalov Vladimir J VJ Jacobson Samuel G SG Cideciyan Artur V AV Palczewski Krzysztof K

Human molecular genetics 20150224 11

Mutations in the ABCA4 gene are a common cause of autosomal recessive retinal degeneration. All mouse models to date are based on knockouts of Abca4, even though the disease is often caused by missense mutations such as the complex allele L541P;A1038V (PV). We now show that the PV mutation causes severe human disease whereas the V mutation alone causes mild disease. Mutant ABCA4 proteins expressed heterologously in mammalian cells retained normal cellular localization. However, basal and all-tra ...[more]

PMID: 25712131

Similar Datasets

Yap and Taz regulate retinal pigment epithelial cell fate

Project description:The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Teadresponsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosagedependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson’s chorioretinal atrophy and congenital retinal coloboma. 60 pooled eyes from 36 hpf wild type or vsx2:Gal4/dsRed:14xUAS:YapS87A embryos were pooled for one sample. Three wild type and three vsx2:Gal4/dsRed:14xUAS:YapS87A pools were analyzed for RNA.

2015-08-06 | E-GEOD-71681 | biostudies-arrayexpress

Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration

Project description:To identify disease-specific transcriptional programs in retinal pigment epithelium (RPE) cells, fibroblasts from 43 patients with geographic atrophy (GA) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into RPE and compared to those from 36 healthy individuals. 127,659 RPE cells were profiled via single cell RNA-sequencing (scRNA-seq) and cell classification identified 7 cellular states related to RPE maturation.

2022-06-20 | E-MTAB-11642 | biostudies-arrayexpress

Identification of miRNA signatures during the differentiation of hESCs into retinal pigment epithelial cells

Project description:Retinal pigment epithelium (RPE) cells can be obtained through in vitro differentiation of both embryonic stem cell (ESC) and induced pluripotent stem cells (iPSC) for cell replacement therapy. We have previously identified 87 signature genes relevant to RPE cell differentiation and function through transcriptome analysis of both human ESC- and iPSC-derived RPE as well as normal fetal RPE. Here, we profiled miRNA expression through small RNA-seq in human ESCs and their RPE derivatives. Much like conclusions drawn from our previous transcriptome analysis, we found that the overall miRNA landscape in RPE is distinct from ESCs and other differentiated somatic tissues. We also profiled miRNA expression during intermediate stages of RPE differentiation and identified unique subsets of miRNAs that are gradually up- or downregulated, suggesting dynamic regulation of these miRNAs is associated with the RPE differentiation process. Indeed, the down-regulation of a subset of miRNAs during RPE differentiation is associated with up-regulation of RPE-specific genes, such as RPE65, which is exclusively expressed in RPE. We conclude that miRNA signatures can be used to classify different degrees of in vitro differentiation of RPE from human pluripotent stem cells. We suggest that RPE-specific miRNAs likely contribute to the functional maturation of RPE in vitro, similar to the regulation of RPE-specific mRNA expression. Study miRNA in ESC-derived RPE

2012-08-01 | E-GEOD-37686 | biostudies-arrayexpress

Pigment Epithelium Derived Factor (PEDF) secreted from iPSC derived-RPE facilitates apoptotic causes cell death, not the differentiation, of iPSCs

Project description:We show that Retinal pigment epithelium (RPE) secreted-factor, pigment epithelium derived factor (PEDF) secreted/derived from primary or iPSC-derived retinal pigment epithelium (RPE)RPE, dramatically inhibitsed the cell growth of iPSCs. PEDF was detected abundantly in culture supernatant media of primary and iPSC-derived RPE. We examined the gene expression in primary RPE and iPS-derived RPE. Two samples: RPE derived from 253G1 iPSC, Primary RPE.

2013-01-03 | E-GEOD-43257 | biostudies-arrayexpress

Proteome landscape of epithelial to mesenchymal transition (EMT) of retinal pigment epithelium shares commonalities with malignancy-associated EMT

Project description:Retinal pigment epithelium (RPE) stress and injury often leads to epithelial to mesenchymal transition (EMT), in which RPE cells lose its cobblestone morphology and acquire more motile and spindle-shaped fibroblast phenotype. RPE dysfunction due to acquired EMT phenotype have been implicated in a number of retinal diseases such as proliferative vitreoretinopathy (PVR), diabetic retinopathy (DR), neovascular (“wet”) and atrophic (“dry”) age-related macular degeneration (AMD). We investigated distinct temporal protein expression changes and signaling events that occur during enzymatically dissociated hRPE EMT model, as well as those that occur up to forty-eight hours after EMT onset. Further, we compared analysis on altered proteome profiling with malignancy associated EMT and AMD models. Together, proteome profiles provide a comprehensive RPE EMT resources for understanding molecular signaling events, associated biological pathways, that underlie RPE-EMT onset and further identifying chemical modulators that could potentially inhibit RPE EMT.

2021-09-21 | PXD019600 | Pride

RNAseq analysis of the global bovine retinal transcriptome

Project description:We report RNAseq analysis of the transcriptome of 3 biological replicates of bovine retina Examine retinal transcriptome of 3 biological replicates with tissue collected between 7:00 - 10:00AM

2014-09-10 | E-GEOD-59911 | biostudies-arrayexpress

cultured RPE phosphpproteome - Quantitative phosphoproteomics reveals involvement of multiple signaling pathways in early phagocytosis by the retinal pigmented epithelium

Project description:One of the major biological functions accomplished by the retinal pigmented epithelium (RPE) is the clearance of shed photoreceptor outer segments (POS) through a multistep process referred to as phagocytosis. Phagocytosis helps maintain the viability of photoreceptors which otherwise could succumb to the high metabolic flux and photo-oxidative stress associated with visual processing. Regulatory mechanisms underlying phagocytosis in the RPE are not fully understood, although dysfunction of this process contributes to the pathogenesis of multiple human retinal degenerative disorders, including age-related macular degeneration (AMD). Here we present an integrated analysis of phagocytosing cultured-RPE cells.

2017-10-27 | PXD006144 | Pride

The transcriptional response to Norrin/Fz4 signaling

Project description:Using mice with targeted gene mutations, we identify (1) distinct roles for different canonical Wnt signaling components in central nervous system (CNS) vascular development and in the specification of the blood-brain and blood-retina barriers (BBB and BRB) and (2) differential sensitivities of the vasculature in various CNS regions to perturbations in canonical Wnt signaling components. We find nearly equivalent roles for Lrp5 and Lrp6 in brain vascular development and barrier maintenance but a dominant role for Lrp5 in the retinal vasculature, an especially high sensitivity of the BBB in the cerebellum and pons/interpeduncular nuclei to decrements in canonical Wnt signaling, and plasticity in the barrier properties of mature CNS vasculature. Brain and retinal vascular defects caused by loss of Norrin/Frizzled4 signaling can be fully rescued by stabilizing beta-catenin, and loss of beta-catenin’s transcriptional activation domain or expression of a dominant negative Tcf4 recapitulates the vascular development and barrier defects seen with loss of receptor, co-receptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly by beta-catenin-dependent transcriptional regulation. This work strongly supports a model in which identical or nearly identical canonical Wnt signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB. Total retina RNA from P10 WT, NdpKO, Ctnnb1flex3/+;Pdgfb-CreER, and NdpKO;Ctnnb1flex3/+;Pdgfb-CreER mice was subjected to RNAseq

2014-06-05 | E-GEOD-56461 | biostudies-arrayexpress

Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in Adiponectin receptor 1 (AdipoR1) deficient mice

Project description:Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration (AMD). This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 FAs, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α (PPARα) signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium (RPE). Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome (BBS) proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in BBS-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including AMD.

2024-06-23 | PXD050916 | Pride

Integrated analysis of DNA methylation and RNA transcriptome during the differentiation of human pluripotent stem cells into retinal pigment epithelial cells

Project description:Using the paradigm of in vitro differentiation of hESCs/iPSCs into retinal pigment epithelial (RPE) cells, we have recently profiled mRNA and miRNA transcriptomes to define a set of RPE mRNA and miRNA signature genes implicated in directed RPE differentiation. In this study, in order to understand the role of DNA methylation in RPE differentiation, we profiled genome-scale DNA methylation patterns using the method of reduced representation bisulfite sequencing (RRBS). We found dynamic waves of de novo methylation and demethylation in four stages of RPE differentiation. Integrated analysis of DNA methylation and RPE transcriptomes revealed a reverse-correlation between levels of DNA methylation and expression of a subset of miRNA and mRNA genes that are important for RPE differentiation and function. Gene Ontology (GO) analysis suggested that genes undergoing dynamic methylation changes were related to RPE differentiation and maturation. We further compared methylation patterns among human ESC- and iPSC-derived RPE as well as primary fetal RPE (fRPE) cells, and discovered that specific DNA methylation pattern is useful to classify each of the three types of RPE cells. Our results demonstrate that DNA methylation may serve as biomarkers to characterize the cell differentiation process during the conversion of human pluripotent stem cells into functional RPE cells. Study of DNA methylation patterns during RPE differentiation of pluripotent stem cells.

2014-05-28 | E-GEOD-43473 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data