PD1-mediated microglia assisted cerebrovascular pruning during vascular development.
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ABSTRACT:
PROVIDER: PRJNA1157222 | ENA |
REPOSITORIES: ENA
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Project description:To further explore the mechanism of cerebrovascular pruning by PD1 in microglia, we analyzed RNA isolated from Pd1fl/fl and Pd1cKO-Cx3 cerebral cortical microglia at P11 using RNA-seq to identify genome-wide changes.
2024-09-10 | GSE276402 | GEO
Project description:Purpose: To explore further into the mechanisms by which endothelial PD1 controls cerebrovascular development and oligodendrogenesis, we employed RNA-seq to examine genome-wide alterations in endothelial cells from P0 conditional PD1 knockout mice, comparing them with their wild-type littermates. Methods: mRNA was extracted from P0 isolated endothelial cells of Pd1fl/fl and Pd1cKO-Tie2 mice, and the quality and quantity were assessed using the Agilent 2100 Bioanalyzer. Subsequently, the mRNA was converted to cDNA and Libraries were prepared. RNA-sequencing was performed on the Illumina HiSeq 2500 platform at Annoroad Genomics. Results: Approximately one thousand transcripts showed differential expression between the Pd11fl/fl and Pd1cKO-Tie2 mice brain endothelial cell, with a fold change ≥2 and p value <0.05.Geneontology analysis of the downregulated genes were enriched in terms related to positive regulation of angiogenesis, positive regulation of vascular endothelial growth factor production and positive regulation of inflammatory response. Concomitantly, upregulated genes were enriched in terms related to endothelial cell migration, sequestering of BMP from receptor via BMP binding and regulation of establishment of blood-brain barrier. These results reflected endothelial PD1 plays vital roles in cortex development. Conclusions: Endothelial PD1 RNA-seq would provide a overall understanding how endothelium-derived PD1regulates vessel development and oligodendrogenesis during brain development
2024-05-13 | GSE267172 | GEO
Project description:Recent success in cancer immunotherapy has come from the blockade of inhibitory receptors on T cells, such as programmed cell death-1, which can induce a state of T cell exhaustion upon constant antigen stimulation. Understanding miRNA regulation of PD1 can be useful to discover miRNAs for use in therapy or as prognostic markers in various diseases including cancer, autoimmunity and transplantation. We used microarrays to discover global miRNA expression changes upon PD1 upregulation and identified miRNAs that are both up- and down-regulated. B16F10 cells were injected subcutaneously into C57BL/6 mice and 16 days later CD4+PD1+ and CD4+PD1- were sorted from the lymph nodes and spleen for RNA extraction and hybridization on Affymetrix miRNA array.
2015-08-01 | E-GEOD-65208 | biostudies-arrayexpress
Project description:CMKLR1 in Vascular Smooth Muscle Cells: A Therapeutic Focus for Cardiovascular and Cerebrovascular Diseases
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Project description:Cerebrovascular injuries can cause severe edema and inflammation that adversely affect human health. Here, we observed recanalization after successful endovascular thrombectomy for acute large vessel occlusion was associated with cerebral edema and poor clinical outcomes in patients who experienced hemorrhagic transformation. To understand this process, we developed a cerebrovascular injury model using transcranial ultrasound that enabled spatiotemporal evaluation of resident and peripheral myeloid cells. We discovered that injurious and reparative responses diverged based on time and cellular origin. Resident microglia initially stabilized damaged vessels in a purinergic receptor-dependent manner, which was followed by influx of myelomonocytic cells that caused severe edema. Prolonged blockade of myeloid cell recruitment with anti-adhesion molecule therapy prevented severe edema but also promoted neuronal destruction and fibrosis by interfering with vascular repair later orchestrated by pro-inflammatory monocytes and pro-angiogenic repair-associated microglia (RAM). These data demonstrate how temporally distinct myeloid cell responses can contain, exacerbate, and ultimately repair a cerebrovascular injury.
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Project description:Transcriptome changes were also examined at three stages of SAM self-pruning utilizing microarray. Combining results from different stages, 1,573 differentially expressed genes were identified; the extensive repertoire of genes associated with programmed cell death, cell wall biosynthesis and metabolism strongly suggests that abscission layers activate both catabolic and anabolic wall modification pathways during self-pruning process. Three independent citrus RNA samples (Three days before self-pruning, begin self-pruning and seven days after self-pruning) were hybridized with microarrays separately
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Project description:Functional impairment of the immune response to chronic viral infections and malignancies is characterised by exhausted T cells, which do not respond to antigen. The cell surface receptor PD1 has been implicated in the maintenance of T cell exhaustion and is an attractive target for immunomodulatory approaches to the treatment of such conditions. However, the mechanisms by which PD1 signalling causes exhaustion and the exact response of T cells to PD1 activation are not clear although it has been suggested that PD1 up regulates a number of anti-proliferative factors. Here we perform cytokine and transcriptional profiling of uninfected primary human T cells to characterise these events. We find that PD1 completely prevents cytokine and transcrip- tional changes induced by CD3/28 stimulation. We do not see any factors specifically induced by PD1, including BATF or IL10 which have previously been linked to PD1 activity. Together with the work of others this confirms that PD1 is the sole effector of T cell exhaustion and that infection is responsible for BATF and IL10 up regulation. As a consequence future therapeutic strategies will be confined to the inhibition of PD1 and not a downstream effector.
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Project description:We have identified a CD57+PD1- CD4 T cell phenotype at the time of transplantation that strongly correlates with subsequesnt development of belatacept-resistant rejection. In this study, we used microarray to determine which genes were upregulated in CD57+ compared to CD57- CD4 T cells. Peripheral blood obtained from 5 healthy controls was processed and sorted into CD4+CD57+PD1- and CD4+CD57-PD1- populations. Total RNA was extracted from the sorted populations and quality assessed. cDNA synthesis and amplification was performed, and fragmented and biotinylated samples were hybridized to the Affymetrix Human U133 plus 2.0 probe array. The arrays were scanned and probe intensity measurements were normalized across the samples using the robust multichip average (RMA) algorithm.
2016-01-08 | E-GEOD-64805 | biostudies-arrayexpress
Project description:Vascular aging, which is characterized by brain endothelial cell (EC) senescence and dysfunction, is known to contribute to various age-related cerebrovascular and neurodegenerative diseases. However, the underlying mechanisms remain unclear. EC-derived microvesicles (EMVs) and exosomes (EEXs) retain the characteristics of parent cells and transfer their contents to modulate the functions of recipient cells, showing potential for evaluation or regulation of vascular aging. Here, as indicated by analyses of senescence-associated beta-galactosidase (SA-β-gal) staining, cerebral blood flow, blood–brain barrier function, aging-related markers and cognitive ability, we found that young primary EC (passage 2-4) released EMVs alleviated mouse cerebrovascular and brain aging more effectively than EEXs. Aged EC (passage 15-16) released EMVs were more effective than their released EEXs at exacerbating mouse cerebrovascular and brain aging. We further revealed that these EMVs regulated cerebrovascular and brain aging by transferring miR-17-5p and modulated EC senescence and function via the miR-17-5p/PI3K/Akt pathway. Clinically, the levels of plasma EMVs and their associated miR-17-5p (EMV-miR-17-5p) were significantly increased or decreased in elderly individuals and were closely correlated with reactive oxygen species (ROS) and vascular aging. Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) was 0.724 for EMVs, 0.77 for EMV-miR-17-5p and 0.815 for their combination for distinguishing vascular aging. Our results identified novel roles for EMVs and showed that these vesicles more effectively modulated vascular and brain aging than did EEXs by regulating EC functions through the miR-17-5p/PI3K/Akt pathway; thus, EMVs and EMV-miR-17-5p are promising biomarkers and therapeutic targets for vascular aging.
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Project description:We report the gene expression profiles of FACS-sorted PD1-high, PD1-intermediate, and PD1-negative tumor-infiltrating CD8 T cells in hepatocellular carcinoma.
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