Hypoxia tolerance in the Norrin-deficient retina and the chronically hypoxic brain stuied at single-cell resolution
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA517321 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8492100.fastq.gz | Fastqsanger.gz | |||
| SRR8492110.fastq.gz | Fastqsanger.gz | |||
| SRR8492101.fastq.gz | Fastqsanger.gz | |||
| SRR8492111.fastq.gz | Fastqsanger.gz | |||
| SRR8492102.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 23 |
Similar Datasets
Project description:The mammalian central nervous system (CNS) is capable of tolerating chronic hypoxia, but cell type-specific responses to this stress have not been systematically characterized. In the Norrin-knockout (NdpKO) mouse, a model of familial exudative vitreoretinopathy (FEVR), developmental hypovascularization of the retina produces chronic hypoxia of inner nuclear layer (INL) neurons and Muller glia. We have used single-cell RNA sequencing, untargeted metabolomics, and metabolite labeling from 13C-glucose to compare wild type and NdpKO retinas. In NdpKO retinas, we observe gene expression responses consistent with hypoxia in Muller glia and retinal neurons, and we find a metabolic shift that combines reduced flux through the tricarboxylic acid cycle with increased synthesis of serine, glycine, and glutathione. We also used single-cell RNA sequencing to compare the responses of individual cell types in NdpKO retinas to those in the hypoxic cerebral cortex of mice that were housed for one week in a reduced oxygen environment (7.5% oxygen). In the hypoxic cerebral cortex, glial transcriptome responses most closely resemble the response of Muller glia in the NdpKO retina. In both retina and brain, vascular endothelial cells activate a previously dormant tip cell gene expression program, which likely underlies the adaptive neo-angiogenic response to chronic hypoxia. These analyses of retina and brain transcriptomes at single-cell resolution reveal both shared and cell-type-specific changes in gene expression in response to chronic hypoxia, implying both shared and distinct cell type-specific physiologic responses.
2019-04-19 | GSE125708 | GEO
Project description:The mammalian CNS is capable of tolerating chronic hypoxia, but cell type-specific responses to this stress have not been systematically characterized. In the Norrin KO (Ndp KO ) mouse, a model of familial exudative vitreoretinopathy (FEVR), developmental hypovascularization of the retina produces chronic hypoxia of inner nuclear-layer (INL) neurons and Muller glia. We used single-cell RNA sequencing, untargeted metabolomics, and metabolite labeling from 13C-glucose to compare WT and Ndp KO retinas. In Ndp KO retinas, we observe gene expression responses consistent with hypoxia in Muller glia and retinal neurons, and we find a metabolic shift that combines reduced flux through the TCA cycle with increased synthesis of serine, glycine, and glutathione. We also used single-cell RNA sequencing to compare the responses of individual cell types in Ndp KO retinas with those in the hypoxic cerebral cortex of mice that were housed for 1 week in a reduced oxygen environment (7.5% oxygen). In the hypoxic cerebral cortex, glial transcriptome responses most closely resemble the response of Muller glia in the Ndp KO retina. In both retina and brain, vascular endothelial cells activate a previously dormant tip cell gene expression program, which likely underlies the adaptive neoangiogenic response to chronic hypoxia. These analyses of retina and brain transcriptomes at single-cell resolution reveal both shared and cell type-specific changes in gene expression in response to chronic hypoxia, implying both shared and distinct cell type-specific physiologic responses.
| S-EPMC6500147 | biostudies-literature
Project description:Purpose: Bulk RNA-Seq of wild-type mice retina after different hypoxic exposures, to evaluate the influence on retinal pathologies. Methods: Retinal mRNA profiles of C57BL/6J mice after 6 different hypoxic exposures were generated by deep sequencing (n=6) using paired-end high output sequencing (Illumina Novaseq 6000). Results: Longitudinal studies over 11 weeks in normobaric hypoxia revealed four classes of genes that adapted differentially to the long-term hypoxic condition. Many differentially expressed genes were involved in the regulation of gene expression. Seventeen genes were specifically regulated in hypobaric hypoxia. Some of these genes may affect the structural integrity of the retina or individual cells, resulting in the slight shortening of photoreceptor segment length detected in various hypoxic groups.
2021-08-10 | GSE173233 | GEO
Project description:Neuroprotective therapies for retinal degeneration may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. Our data suggest that neuroprotection after hypoxic preconditioning of the retina is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult. Keywords: hypoxic preconditioning, neuroprotection, transcription-profile, retina
2009-01-10 | GSE14366 | GEO
Project description:Neuroprotective therapies for retinal degeneration may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. Our data suggest that neuroprotection after hypoxic preconditioning of the retina is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult. Experiment Overall Design: In total 24 samples were analyzed on Affymetrix mouse 430.2 arrays, the samples represent different durations of regeneration (none = 0 h, 2 h, 4 h and 16 h) from hypoxic or normoxic treatments, that were tested in triplicates.
2009-01-17 | E-GEOD-14366 | biostudies-arrayexpress
Project description:Reduced oxygenation of photoreceptors and the RPE in the ageing eye may be a risk factor for the development of both neovascular and dry AMD. Chronic activation of the molecular response to hypoxia in RPE or photoreceptors leads to retinal degeneration that depends on hypoxia inducible transcription factors. For approaching the identification of accessible markers characteristic for photoreceptors with an activated hypoxic response, we used a proteomics approach to determine the protein composition of the vitreous humor in mice. To discriminate between rod and cone-specific effects we used genetically modified mice that had the hypoxic response activated specifically in rods of a rod-dominant retina (rodΔVhl) or a genetically engineered all-cone retina (coneΔVhl). For comparison, we used wild-type mice exposed for 6 hours to acute hypoxia. We identified 1,357 unique proteins in the vitreous of mice after acute hypoxia, 1,624 in rodΔVhl and 1,895 in coneΔVhl mice. Of these, 1,043 proteins were common to all three types of mice. Of the identified proteins, 257 were significantly regulated by a factor of 1.5 or more in hypoxic mice, 258 in rodΔVhl and 356 in coneΔVhl mice in at least one of the three analyzed time points. Only 51 of the significantly regulated proteins were common to the vitreous of rodΔVhl and coneΔVhl mice, suggesting different consequences of the activated hypoxic response for rods and cones. Guanylate binding protein 2 (GBP2) was found at increased levels in the vitreous of both rodΔVhl and coneΔVhl mice at all time points tested. This was also reflected by increased gene expression in the retina. Although retinal expression of the AMD-associated gene alpha-2 macroglobulin (A2M) appeared increased in both types of mice, the protein was only found elevated in the vitreous of rodΔVhl mice. Other proteins found increased included Serpina3n, synaptosome associated protein 25 (SNAP25) and others. The distinct protein compositions present at early and late time points, suggest a well-regulated process in our models. We hypothesize that some of the proteins identified at early time points may potentially be used as markers for the chronic hypoxic response of photoreceptors.
2019-06-12 | PXD008911 | Pride
Project description:These are two time-series of affymetrix MOE430A microarrays of mouse retina ranging from 7 to 12 days. The two conditions are normoxia and hyperoxia
2008-10-25 | E-GEOD-1816 | biostudies-arrayexpress
Project description:The integrity of the blood–retina barrier (BRB) is crucial for phototransduction and vision, by tightly restricting transport of molecules between the blood and surrounding neuronal cells. Breakdown of the BRB leads to the development of retinal diseases. Here, we show that Netrin-1/Unc5b and Norrin/Lrp5 signaling establish a zonated endothelial cell gene expression program that controls BRB integrity. Using single-cell RNA sequencing (scRNA-seq) of postnatal BRB-competent mouse retina endothelial cells (ECs), we investigate >100 BRB genes encoding Wnt signaling components, tight junction proteins, and ion and nutrient transporters. We find that BRB gene expression is zonated across arteries, capillaries, and veins and regulated by opposing gradients of the Netrin-1 receptor Unc5b and Lrp5-β-catenin signaling between retinal arterioles and venules. Mice deficient for Ntn1 or Unc5b display more BRB leakage at the arterial end of the vasculature, while Lrp5 loss of function causes predominantly venular BRB leakage. ScRNA-seq of Ntn1 and Unc5b mutant ECs reveals down-regulated β-catenin signaling and BRB gene expression that is rescued by Ctnnb1 overactivation, along with BRB integrity. Mechanistically, we demonstrate that Netrin-1 and Norrin additively enhance β-catenin transcriptional activity and Lrp5 phosphorylation via the Discs large homologue 1 (Dlg1) scaffolding protein, and endothelial Lrp5-Unc5b function converges in protection of capillary BRB integrity. These findings explain how arteriovenous zonation is established and maintained in the BRB and reveal that BRB gene expression is regulated at the level of endothelial subtypes.
2024-12-03 | GSE282775 | GEO
Project description:Interventions: Group 1: The EC@T-project consists of three substudies: two qualitative and one quantitative study. In all three studies there will be two sample groups, providers and chronically ill patients (see fulfilling one of the diagnoses). First, within the qualitative study we will interview the attitudes of patients and providers and we are planning to generate items for the EC@T questionnaire. Then all participants will fill out the questionnaire.
Primary outcome of the project is to develop the EC@T questionnaire based on interview data and analysis of literature. aim: measurement of attitudes towards eCommunication of providers and chronically ill patients.
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: other
| 2430027 | ecrin-mdr-crc
Project description:Restricted oxygen supply from the choroid may lead to hypoxic conditions in the outer retina of the ageing eye and contribute not only to physiological aging but also to nonhereditary degenerative retinal diseases. To understand the hypoxic response of specific retinal cell types, we performed droplet-based single-cell RNA sequencing (scRNA-Seq) of retinas isolated from mice exposed to hypoxia. Except for ganglion cells, we identified all retinal cell types and a small RPE cluster among the 9410 normoxic and 9033 hypoxic cells in the analysis. Expression of hypoxic marker genes including Bnip3, Higd1a, and Egln1 was significantly upregulated in hypoxic clusters, confirming a general transcriptional response to hypoxia. Interestingly, RNA-binding proteins Rbm3 and Cirbp were differentially expressed across clusters and demonstrated isoform switching in hypoxia. The resulting short variants of these gene transcripts are connected to epitranscriptomic regulation, a notion supported by the differential expression of writers, readers and erasers of m 6 A RNA methylations in the hypoxic retina. By focusing on the hypoxic response in photoreceptors, we identified and confirmed a kinesin motor protein (Kif4) that was specifically and strongly induced in hypoxic cones. Retinal cells adapted to hypoxic conditions by adjusting their gene expression profile. Epitranscriptomic regulation of m 6 A RNA methylations may support the adaptational process. The cone-specific upregulation of Kif4, a motor protein with multiple functions, indicated a cone-specific response to hypoxia that may include cargo-delivery to specific intracellular locations, enrichment of transmembrane receptors or channels and/or modulation of chromatin structure.
2024-12-03 | GSE242982 | GEO