Rb knockout retinal explant comparison
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE1129 | GEO | 2004/03/16
SECONDARY ACCESSION(S): PRJNA87241
REPOSITORIES: GEO
Similar Datasets
Project description:knockout and wildtype sample pair Keywords = rod Keywords = retina Keywords = mouse Keywords = Rb
2010-06-09 | E-GEOD-1129 | biostudies-arrayexpress
Project description:The absence of the Rb tumor suppressor gene changes levels/activities of transcription factors (e.g., E2F and p53) which alter gene expression patterns, related to cell cycle control and cellular response to DNA damage. Cisplatin is a genotoxic chemotherapeutic agent and wildtype or Rb null cells have different sensitivities to cisplatin-induced cytotoxicity. We used microarrays to compare global profiles of gene expression and distinct responses of wildtype and Rb null MEFs in response to cisplatin. Keywords: genotype and cisplatin treatment
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Project description:Bhlhe23 is a transcription factor that is required for the maturation and survival of retinal rod bipolar cells in mice. In the adult Bhlhe23-/- retina, rod bipolar cells are almost completely absent. We identified genes that were likely to be important to rod bipolar cell maintenance and function by identifying genes that were significantly down-regulated in the transcriptome of adult Bhlhe23-/- mouse retina compared with wild type retina.
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Project description:Rod and cone photoreceptors in mammalian retina are generated from common pool(s) of neuroepithelial progenitors. NRL, CRX and NR2E3 are key transcriptional regulators that control photoreceptor differentiation. Mutations in NR2E3, a rod-specific orphan nuclear receptor, lead to loss of rods, increased density of S-cones, and supernormal S-cone-mediated vision in humans. To better understand its in vivo function, NR2E3 was expressed ectopically in the Nrl-/- retina, where post-mitotic precursors fated to be rods develop into functional S-cones similar to the human NR2E3 disease. Expression of NR2E3 in the Nrl-/- retina completely suppressed cone differentiation and resulted in morphologically rod-like photoreceptors, which were not functional. Gene profiling of FACS-purified photoreceptors confirmed the role of NR2E3 as a strong suppressor of cone genes and an activator of a subset of rod genes (including rhodopsin) in vivo. Ectopic expression of NR2E3 in cone precursors and differentiating S-cones of wild type retina also generates rod-like cells. The dual regulatory function of NR2E3 is not dependent upon the presence of NRL and/or CRX, but on the timing and level of its expression. Our studies reveal a critical role of NR2E3 in establishing functional specificity of post-mitotic photoreceptor precursors during retinal neurogenesis. Keywords: genetic modification
2006-08-18 | GSE5338 | GEO
Project description:The absence of the Rb tumor suppressor gene changes levels/activities of transcription factors (e.g., E2F and p53) which alter gene expression patterns, related to cell cycle control and cellular response to DNA damage. Cisplatin is a genotoxic chemotherapeutic agent and wildtype or Rb null cells have different sensitivities to cisplatin-induced cytotoxicity. We used microarrays to compare global profiles of gene expression and distinct responses of wildtype and Rb null MEFs in response to cisplatin. Experiment Overall Design: Primary wildtype or Rb null MEFs were generated from embryos at embryonic day 13.5 and cultured to passage 2. Wildtype or Rb null MEFs were either untreated or treated with 16 microM cisplatin for 24 hours prior to harvest and RNA extraction. Four different RNA samples (wildtype or Rb-/- MEFs, untreated or cisplatin-treated) were used for hybridization in triplate to Affimatrix Chips. Then, the total of 12 hybridizations were divided into 4 subseries: UT-Rb, UT-WT, CP-Rb, CP-Wt, and each subseries contained three samples (hybridization 1-3 or a-c).
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Project description:Amycolatopsis mediterranei RB strain:RB Genome sequencing
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Project description:To better understand the mechanistic basis of aging and its relationship with retinal degeneration, we examined gene expression changes in aging rod photoreceptors. Rod photoreceptor cell death is a feature of normal retinal aging and is accelerated in many retinal degenerative diseases, including AMD, the leading cause of untreatable adult blindness in the United States and other western countries. To our knowledge, the examination of age-related gene expression changes in a specific neuronal cell-type is novel, and it has allowed us to identify significant age-related changes with better resolution than is possible with whole retina samples. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR. Our results suggest that aging is progressive, beginning even in young adult mice. Although rod photoreceptors are highly specialized neurons, our analyses revealed changes in consensus pathways of aging, including oxidative phosphorylation and stress responses affecting transcription and inflammation. In addition, we identified stress response processes that may be especially relevant for the aging retina and retinal diseases, such as angiogenesis and nuclear receptor signaling pathways that affect retinoid and lipid metabolism. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR.
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Project description:From 3 months of age the retina is known to undergo morphoplogical remodelling. This analysis examines expression in the retina after all the rod photoreceptors are lost (by 1 month) and compares the changes in expression that occur before (2 months) and after (8 months) remodelling. Total RNA was extracted from central retina regions by punch biopsy at 2 months and 8 months of age from C57Bl6/rd1 mice.
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Project description:Gene expression of Retinoblastoma deficient mouse embryonic fibroblasts (Rb-/- MEF, ME3) and wildtype mouse embryonic fibroblasts (Rb+/+ MEF,MEFA) during adipocyte differentiation were studied by cDNA microarray analysis. 2-day postconfluent cells (day 0) were treated with a hormonal cocktail including Rosiglitzone for differentiation into adipocytes. Gene expression at day 1, day 3, and day 8 after hormonal induction were compared to that before induction (day 0).
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Project description:The nuclei of rod photoreceptors in mice and other nocturnal species have an unusual inverted chromatin structure with centrally located heterochromatin that helps to focus light and improve photosensitivity. To gain a deeper understanding of this unique nuclear organization of rod photoreceptors, we have carried out Hi-C on retina at 3 stages of development and on purified rod photoreceptors. Predicted looping interactions from the Hi-C data were validated with fluorescent in situ hybridization (FISH). We discovered that a subset of genes important for retinal development, cancer and stress response in the retina are localized to the facultative heterochromatin domain in a developmental stage– and cell type–specific manner. We used machine learning to develop an algorithm based on our chromatin Hidden Markov Modeling (chromHMM) of retinal development to predict heterochromatin domains and study their dynamics during retinogenesis. FISH data for 264 genomic loci were used to train and validate the algorithm. These integrated data (https://pecan.stjude.cloud/retinalnucleome) were used to identify a developmental stage- and cell type-specific core regulatory circuit super-enhancer (CRC-SE) upstream of the Vsx2 gene that is required for bipolar neuron expression. Deletion of the Vsx2 CRC-SE in mice led to the loss of bipolar neurons in the retina.
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