Goals/objectives: to identify various gene expression in B cell subsets derived from human PBMC and cord blood
Differential expression of CD21 identifies developmentally and functionally distinct subsets of human transitional B cells.
Specimen part
View SamplesHuman herpesvirus-8 (HHV-8) is the causative agent of Kaposis sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma (PEL) and multicentric Castlemans disease (MCD). We have previously described evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH). We speculated that viral infection of the pulmonary microvascular endothelial cells could cause the angioproliferative phenotype characteristic of severe pulmonary arterial hypertension (PAH). We now demonstrate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells (HPMVECs) in vitro, confirming both latent and lytic infection. HHV-8 infection of HPMVECs resulted in significant changes of gene expression including alterations of pathways integral to both cellular apoptosis and angiogenesis. This infection also results in alterations of genes integral to the bone morphogenic protein (BMP) pathway, including down regulation of bone morphogenic protein receptor 1a (BMPR1a) and bone morphogenic protein 4 (BMP4). Other genes previously implicated in the development of PAH are also altered in expression by HHV-8 infection. These include increased expression of Interleukin-6 (IL-6) and the matrix metalloproteinases (MMP)-1, MMP-2 and MMP-10. Lastly, cells infected with HHV-8 apoptosis resistant. Infection of pulmonary microvascular endothelial cells with human herepesvirus-8 results in alteration of the BMP pathway as well as an anti-apoptotic phenotype, consistent with the development of plexiform lesions characteristic of pulmonary arterial hypertension.
Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells.
No sample metadata fields
View SamplesCaspase-1 activation senses metabolic danger-associated molecular patterns and mediates the initiation of inflammation. Here, we reported that caspase-1 contributes to hyperlipidemia-induced modulation of vascular cell gene expression during early atherosclerosis in vivo. Our results demonstrate the therapeutic potential of caspase-1 inhibition in the treatment of cardiovascular diseases.
Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation.
Sex, Age, Specimen part
View SamplesInterleukin-17 (IL-17)-secreting T helper 17 cells (Th17) are a recently identified CD4+ T helper subset that has been implicated in various inflammatory and autoimmune diseases. The issue of whether interleukin-17A (IL-17) contributes to hyperlipidemia-induced aortic endothelial cell activation remained unknown. Here, we reported that IL-17 contributes to hyperlipidemia-induced modulation of vascular cell gene expression during early atherosclerosis in vivo. Our results has shed lights onto the role of IL-17 on EC biology and has provided important insights for future development of novel therapeutics for early intervention of cardiovascular diseases and other inflammatory diseases.
Interleukin-17A Promotes Aortic Endothelial Cell Activation via Transcriptionally and Post-translationally Activating p38 Mitogen-activated Protein Kinase (MAPK) Pathway.
Sex, Age, Specimen part
View SamplesMany neural progenitor cells present in the fetus, but also in adult brain, which play a major role for the reproduction for healingin regeneration of neuronal cells, when differentiated cells are damaged. However, effects of radiation effect on undifferentiated neural progenitor cells remained unclear. The radiation doses of medical exposure, pollution by nuclear power plant accidents, and other exposure of workers; medical workers, airline crews, and astronaut have been focused. In this study, we report the effects of low- to middle- dose doses of radiation on cultured human neural progenitor cells (hNPC) differentiated derived from embryonic stem (ES) cells, which are partially compared with those of human umbilical vein endothelial cell (HUVEC).
Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.
Specimen part, Cell line
View SamplesZika virus (ZIKV) is responsible for a major current outbreak in the Americas and has been causally associated with fetal microcephaly as well as Guillain-Barre syndrome in adults. However, the immune responses associated with controlling ZIKV replication remain poorly characterized. Here we report a detailed analysis of innate and adaptive immune responses following ZIKV infection in 16 rhesus monkeys. A robust proinflammatory innate immune response was observed within the first few days of infection, including upregulation of type 1 interferon, which correlated directly with viral loads. Immunomodulatory pathways, including IL-10 and TGF-, were also upregulated. ZIKV-specific neutralizing antibodies emerged rapidly by day 7 and correlated inversely with viral loads, which were undetectable in peripheral blood by day 6-10. In contrast, virus replication persisted in cerebrospinal fluid (CSF) for at least 21-42 days in 75% (3 of 4) of the monkeys that received the lowest dose of ZIKV tested, and ZIKV-specific antibodies were essentially undetectable in CSF. These data suggest that antibodies play a critical role in the rapid control of acute viremia in the periphery but were largely excluded from the central nervous system, allowing viral persistence at this immuonoprivileged site.
Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys.
Time
View SamplesBulk RNA sequencing data from neural progenitor cells under conditions of low or high growth factor and Notch pathway activation Overall design: Cells were treated with high (20 ng/ml EGF and FGF) or low (0.5 ng/ml EGF) recombinant growth factors, with or without Notch pathway inhibitor (DAPT, 10 uM) for 12h.
<i>Cis-</i>activation in the Notch signaling pathway.
Specimen part, Subject
View SamplesThe complete transcriptomes of kidney cortex from 3 ?-HIF2aM3 18 month old TG+ male mice and 3 age matched wild type (WT) C57BL/6 male mice were sequenced on an Illumina HiSeq2000 Sequencer. Overall design: Examination of complete transcriptome of kidney cortex between ?-HIF2aM3 TG+ male mice and wild type C57BL/6 male mice
Activation of HIF2α in kidney proximal tubule cells causes abnormal glycogen deposition but not tumorigenesis.
Sex, Specimen part, Cell line, Subject
View SamplesAlterations in the composition of the gut microbiome have an emerging role in brain function and behaviour. We have porposed that short chain fatty acids (SCFA) including propionate and butyrate which are present in the diet and are fermantation products of many gastrointestinal bacteria are contributing environmental factors in autism spectrum disorders (ASD). Here we used the microarray technology to compare global changes in gene expression profiles following exposure of PC12 cells to structurally related SCFA propionate and butyrate each in two different concentrations. Large number of affected genes, common for both SCFA were identified, including genetic networks and GO processes implicated in ASD.
Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.
Specimen part
View SamplesEGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of -catenin in EGFR TKI resistance has been previously reported however the precise mechanism by which -catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of -catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call adaptive persisters. We previously reported that EGFR-TKI treatment rapidly activates Notch3, and here describe the physical association of Notch3 with -catenin, leading to increased stability and activation of -catenin. We demonstrate that the combination of EGFR-TKI and a -catenin inhibitor inhibits the development of these adaptive persisters, decreases tumor burden, improves recurrence free survival, and overall survival in xenograft models. These results supports combined EGFR-TKI and -catenin inhibition in patients with EGFR mutant lung cancer.
Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC.
Specimen part, Cell line
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