Dendrimer-targeted immunosuppression of microglia reactivity further enhances promotes photoreceptor regeneration kinetics in the zebrafish retina
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PROVIDER: PRJNA891853 | ENA |
REPOSITORIES: ENA
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Project description:We used a zebrafish model of inducible rod photoreceptor death and investsgate the effect of Dexamethasone and nanoparticle-conjugated Dex on regeneration kinetics
2022-10-25 | GSE216060 | GEO
Project description:Purpose: Avian photoreceptors are a diverse class of neurons, comprised of four single cones, the two members of the double cone, and rods. Many distinctive features of photoreceptor subtypes, including spectral tuning, oil droplet size and pigmentation, synaptic targets and spatial patterning, have been well characterized, but the molecular mechanisms underlying these attributes have not been explored. Furthermore, the signaling events and transcriptional regulators driving the differentiation of these diverse photoreceptors are currently unknown. Methods: To identify genes specifically expressed in distinct chicken (Gallus gallus) photoreceptor subtypes, we developed fluorescent reporters that label photoreceptor subpopulations, isolated these subpopulations using fluorescence-activated cell sorting, subjected them to next-generation sequencing, and conducted differential expression analysis. Results: We identified hundreds of differentially expressed genes from photoreceptor subpopulations labeled with rhodopsin, red opsin, green opsin, and violet opsin reporters. These genes are involved in a variety of processes, including phototransduction, transcriptional regulation, cell adhesion, maintenance of intra- and extra-cellular structure, and metabolism. Of particular note are a variety of differentially expressed transcription factors, which may drive and maintain photoreceptor diversity, and cell adhesion molecules that may mediate spatial patterning of photoreceptors and act to establish retinal circuitry. Conclusions: These analyses provide a framework for future studies that will dissect the role of these various factors in the differentiation of avian photoreceptor subtypes. mRNA expression profiling of 5 pairs of photoreceptor subtypes isolated from chicken retinal explants, 3 replicates per sample
2014-09-01 | E-GEOD-59850 | biostudies-arrayexpress
Project description:DNA methylation likely plays a role in the regulation of human stress reactivity. In a genome-wide analysis of blood DNA methylation in 85 healthy individuals a locus in the Kit ligand (KITLG) gene (cg27512205) had the strongest association with cortisol stress reactivity (p=5.8x10-6). Replication was obtained in two independent samples, one using blood (N=45, p=0.001) and the other using buccal cells (N=255,p=0.004). KITLG methylation strongly mediated the relationship between childhood trauma and cortisol stress reactivity (32% mediation). Its genomic location (CpG island shore within an H3K27ac enhancer mark) provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability. Bisulphite converted DNA from whole blood of 85 healthy controls exposed to psychosocial stress task (TSST-G) was hybridised to the Illumina Infinium 450k Human Methylation Beadchip The DOI for this paper will be 10.1038/NCOMMS10967.
2016-03-16 | E-GEOD-77445 | biostudies-arrayexpress
Project description:To explore the diverse platelet microRNA (miRNA) expression between high platelet reactivity (HPR) and low platelet reactivity (LPR) patients with acute coronary syndromes (ACS), we enrolled a cohort of ACS patients and performed miRNA expression profiling of platelets from four HPR and four LPR patients using human miRNA microarray system. VerifyNow P2Y12 assay was applied to indentify HPR and LPR. Venous blood was drawn from the patients and was centrifuged to prepare platelets. Among the candidate differentially expressed miRNAs, miR-15b expression was further confirmed to be lower in platelets of 22 HPR patients than 17 LPR by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). We enrolled a consecutive cohort of 290 ACS patients and assessed the platelet reactivity using VerifyNow P2Y12 assay. In this study, HPR was defined as M-bM-^IM-%300 platelet reactivity unit (PRU) while LPR <170 PRU. miRNA microarray analysis was performed in platelets of four HPR and four LPR patients with ACS.
2014-07-17 | E-GEOD-59488 | biostudies-arrayexpress
Project description:Purpose: Avian photoreceptors are a diverse class of neurons, comprised of four single cones, the two members of the double cone, and rods. Many distinctive features of photoreceptor subtypes, including spectral tuning, oil droplet size and pigmentation, synaptic targets and spatial patterning, have been well characterized, but the molecular mechanisms underlying these attributes have not been explored. Furthermore, the signaling events and transcriptional regulators driving the differentiation of these diverse photoreceptors are currently unknown. Methods: To identify genes specifically expressed in distinct chicken (Gallus gallus) photoreceptor subtypes, we developed fluorescent reporters that label photoreceptor subpopulations, isolated these subpopulations using fluorescence-activated cell sorting, subjected them to next-generation sequencing, and conducted differential expression analysis. Results: We identified hundreds of differentially expressed genes from photoreceptor subpopulations labeled with rhodopsin, red opsin, green opsin, and violet opsin reporters. These genes are involved in a variety of processes, including phototransduction, transcriptional regulation, cell adhesion, maintenance of intra- and extra-cellular structure, and metabolism. Of particular note are a variety of differentially expressed transcription factors, which may drive and maintain photoreceptor diversity, and cell adhesion molecules that may mediate spatial patterning of photoreceptors and act to establish retinal circuitry. Conclusions: These analyses provide a framework for future studies that will dissect the role of these various factors in the differentiation of avian photoreceptor subtypes.
2014-09-01 | GSE59850 | GEO
Project description:DNA methylation likely plays a role in the regulation of human stress reactivity. In a genome-wide analysis of blood DNA methylation in 85 healthy individuals a locus in the Kit ligand (KITLG) gene (cg27512205) had the strongest association with cortisol stress reactivity (p=5.8x10-6). Replication was obtained in two independent samples, one using blood (N=45, p=0.001) and the other using buccal cells (N=255,p=0.004). KITLG methylation strongly mediated the relationship between childhood trauma and cortisol stress reactivity (32% mediation). Its genomic location (CpG island shore within an H3K27ac enhancer mark) provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability.
2016-03-16 | GSE77445 | GEO
Project description:Photoreceptor cell death is a major cause of incurable vision loss in retinal degeneration, with little to no treatment options available. To identify drug candidates to maintain photoreceptor survival, we performed an unbiased high-throughput screening of over 6,000 bioactive small molecules using retinal organoids differentiated from induced pluripotent stem cells of rd16 mice, which phenocopy Leber congenital amaurosis (LCA) 10 caused by CEP290 mutations. Five positive hits including the lead compound Reserpine were further validated by the improvement of photoreceptor maintenance and survival in organoid cultures and in vivo retina. Subsequent investigation revealed misregulation of autophagy in degenerative retina, which is associated with compromised primary cilium biogenesis. Reserpine largely restored the balance between autophagy and the ubiquitin-proteasome system, and improved primary cilium assembly in vitro and in vivo. This study identified effective drug candidates for treatment of retinal degeneration and highlights the impact of proteostasis in photoreceptor cell death.
2023-02-15 | GSE206959 | GEO
Project description:Through a diversity of functional lineages, cells of the innate and adaptive immune system either drive or constrain immune reactions within tumors. Thus, while the immune system has a powerful ability to recognize and kill cancer cells, this function is often suppressed preventing clearance of disease. The transcription factor (TF) BACH2 controls the differentiation and function of multiple innate and adaptive immune lineages, but its role in regulating tumor immunity is not known. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. We found that growth of subcutaneously implanted tumors was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity but was dependent upon adaptive immunity. Analysis of tumor-infiltrating lymphocytes in Bach2-deficient mice revealed high frequencies of CD4+ and CD8+ effector cells expressing the inflammatory cytokine IFN-γ. Lymphocyte activation coincided with reduction in the frequency of intratumoral CD4+ Foxp3+ regulatory T (Treg) cells. Mechanistically, Treg-dependent inhibition of CD8+ T cells was required for BACH2-mediated tumor immunosuppression. These findings demonstrate that BACH2 is a key component of the molecular programme of tumor immunosuppression and identify a new target for development of therapies aimed at reversing immunosuppression in cancer. Analysis of tumor-infiltrating lymphocytes in Bach2-deficient mice revealed high frequencies of CD4+ and CD8+ effector cells expressing the inflammatory cytokine IFN-γ. Lymphocyte activation coincided with reduction in the frequency of intratumoral CD4+ Foxp3+ regulatory T (Treg) cells. Mechanistically, Treg-dependent inhibition of CD8+ T cells was required for BACH2-mediated tumor immunosuppression.
2016-06-01 | E-GEOD-74653 | biostudies-arrayexpress
Project description:Endothelial Rap1B mediates VEGF immunosuppression
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