We used microarrays to detail the global program of gene expression during early hESC differentiation to mesendoderm using FBS, with and without RUNX1 depletion.
Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling.
Specimen part, Cell lineView Samples
We identified 4,356 genes with expression differences associated with a high-fat diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, such as cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Grant: Funding source: American Heart Association Grant number: 16PRE26420105 Title: The effect of maternal over-nutrition on obesity, epigenetics, and gene expression Awarded to Madeline Keleher Overall design: We performed RNA-seq in 21 total libraries, each with two mice of the same sex and diet pooled together (There were 6 low-fat-fed female libraries, 5 libraries of high-fat-fed females, 5 libraries of low-fat-fed males, and 5 libraries of high-fat-fed males). A 1x50 single read sequencing run was done on an Illumina HiSeq 2500 machine (Illumina Inc.)
A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice.
Sex, Specimen part, Cell line, SubjectView Samples
Study on selective vulnerability of certain brain regions to oxidative stress. Here we selected 4 brain regions (hippocampal CA1 and CA3, cerebral cortex, and cerebellar granular layer) to study this phenomenon.
Genomic and biochemical approaches in the discovery of mechanisms for selective neuronal vulnerability to oxidative stress.
Specimen partView Samples
Gender dimorphism exists in the physiological response to diet and other environmental factors. Trans-hydrogenated fatty acid (TFA) intake is associated with an increase in coronary heart disease (CHD), and gender differences in the incidence of CHD are well documented. Neonatal administration of Monosodium Glutamate (MSG) causes stunted heart growth and hypoplasticity; and gender dimorphism at the growth hormone axis has been demonstrated in MSG-treated rodents. The identification of gender dimorphism in cardiac nutrigenomics may provide the basis for gender-specific medicine in the future.
Sex-dimorphism in cardiac nutrigenomics: effect of trans fat and/or monosodium glutamate consumption.
Sex, Specimen partView Samples
We used microarrays to detail the global programme of gene expression during early hESC differentiation to Mesendoderm using FBS.
Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause.
Sex, Cell line, TimeView Samples
Spinal cord injury (SCI) causes severe bone loss and disrupts connections between higher centers in the central nervous system (CNS) and bone. Muscle contraction elicited by functional electrical stimulation (FES) partially protects against loss of bone but cellular and molecular events by which this occurs are unknown. Here, using a rat model, we characterized effects of 7 days of contraction-induced loading of tibia and fibula due to FES when begun 16 weeks after SCI. SCI reduced tibial and femoral BMD by 12-17% and promoted bone resorption, as indicated by increased serum CTX; SCI-related changes in CTX were reversed by FES. In cultures of bone marrow cell-derived cells, SCI increased the number of osteoclasts and mRNA levels of the several osteoclast differentiation markers; these changes were significantly reversed by FES. The number of osteoblasts was also reduced by SCI as was the ratio of OPG/RANKL mRNAs therein; the unfavorable change in OPG/RANKL ratio was partially reversed by FES. cDNA microarray analysis revealed that alterations in genes involved in signaling through Wnt, FSH/LH, PTH and calcineurin/NFAT pathways may be linked to the favorable action of FES on SCI-induced bone resorption. In particular, SCI increased levels of the Wnt inhibitors DKK1, sFRP2 and SOST in osteoblasts, These effects were completely or partially reversed by FES. Our results demonstrate an anti-bone resorptive activity of acute FES in bone loss after SCI and suggest potential underlying mechanisms, among them involving increased Wnt signaling to cause more favorable ratios of OPG and RANKL for the inhibition of osteoclastogenesis. The present study indicates that the effects of bone reloading on SCI- related bone remodeling occurred independently of the effects of higher CNS centers on bone.
The central nervous system (CNS)-independent anti-bone-resorptive activity of muscle contraction and the underlying molecular and cellular signatures.
Sex, Specimen partView Samples
Diarrhea remains a major cause of death in children. Current diagnostic methods largely rely on stool culture and suffer from low sensitivity and inadequate specificity, often leading to inappropriate treatment. The objective of the present study was to use RNA sequencing (RNAseq) analysis to determine blood transcriptional profiles specific for several common pathogenic bacteria and viruses that cause diarrhea in children. We collected whole blood samples from children in Mexico having diarrhea associated with a single pathogen and without systemic complications. Our RNAseq data suggested that the blood signatures can differentiate children with diarrhea from healthy children either with or without bacterial colonization. Moreover, we detected different expression profiles from bacterial and viral infection, demonstrating for the first time the use of RNAseq to identify the etiology of infectious diarrhea. Overall design: 255 whole blood samples from 246 children including children with diarrhea caused by rotavirus (n=60 total; 5 repeated; 55 unique), E.coli (n=55), Salmonella (n=36), Shigella (n=37), adenovirus (n=8), norovirus (n=7), and control children (n=52 total; 4 repeated; 48 unique).
Shared and organism-specific host responses to childhood diarrheal diseases revealed by whole blood transcript profiling.
No sample metadata fieldsView Samples
Lung transplantation remains the only viable therapy for patients with end-stage lung disease; however, full utilization of this treatment strategy is severely compromised by the lack of donor lung availability. For example, the vast majority of donor lungs available for transplantation are obtained from brain death (BD) individuals. Unfortunately, the autonomic storm which accompanies BD often results in neurogenic pulmonary edema (NPE), thereby either producing irreversible lung injury or leading to primary graft dysfunction following lung transplantation. We previously demonstrated that sphingosine 1-phosphate (S1P), a phospholipid angiogenic factor and major barrier-enhancing agent, as well as S1P analogues serve to reduce vascular permeability and ischemia/reperfusion (I/R) lung injury in rodents via ligation of the S1P1 receptor, S1PR1. As primary lung graft dysfunction is induced by lung vascular endothelial cell barrier dysfunction, we hypothesized that SEW-2871, a S1PR1 agonist, may attenuate NPE when administered to the donor shortly after BD. Significant lung injury was observed 4h after BD in a rat BD model with ~60% increases in BAL total protein, BAL cell counts, and lung tissue W/D weight ratios. In contrast, rats receiving SEW-2871 (0.1 mg/kg) 15 minutes after the induction of BD and assessed 4h later exhibited significant lung protection (~50% reduction, p=0.01) reflected by reduced BAL total protein, BAL cytokines concentrations, BAL albumin, BAL total cell count and lung tissue wet/dry (W/D) weights ratio. Microarray analysis at 4hrs revealed a global impact of both BD and SEW on lung gene expression with differential expression of a subclass of genes enriched in immune/inflammation response pathways across the 4 experimental groups. Overall, SEW served to attenuate the BD-mediated ie gene expression upregulation. Two potentially useful biomarkers, Tnf and Ccrl2, exhibited gene dysregulation by microarray analysis, which was validated by qPCR. We conclude that SEW-2871 significantly attenuates BD-induced lung injury and may serve as a potential candidate to improve human lung donor availability and transplantation outcomes.
A sphingosine 1-phosphate 1 receptor agonist modulates brain death-induced neurogenic pulmonary injury.
Sex, Specimen part, TreatmentView Samples
The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. The PfSPZ Vaccine trial in Mali was the first to evaluate the safety and efficacy of this vaccine in a malaria endemic region. Vaccinees received five doses of 2.7 X 105 irradiated sporozoites and the efficacy was measured against naturally occurring Pf Infections in Malian adults during the malaria transmission season. Overall design: 44 samples from 2 time points, pre-vaccination (Day -7) and post-vaccination (Day 143), for 22 Malian adult participants ( 5 placebo controls and 17 vaccine recipients). 11 of the vaccinated participants remained infection free over the subsequent malaria transmission season.
γδ T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations.
Subject, TimeView Samples
Expression profiling was performed using uncultured melanocytes and melanoma cell from various mouse models of BrafV600E induced melanocytic proliferation
mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation.
Specimen partView Samples