Maternal smoking doubles the risk of delivering a low birth weight infant. The purpose of this study was to analyze differential gene expression in umbilical cord tissue as a function of maternal smoking, with an emphasis on growth-related genes. We recruited 15 pregnant smokers and 15 women who never smoked during pregnancy to participate RNA was isolated from umbilical cord tissue collected and snap frozen at the time of delivery. Microarray analysis was performed using the Affymetrix GeneChip Scanner 3000.Six hundred seventy-eight probes corresponding to 545 genes were differentially expressed (i.e., an intensity ratio that exceeded +/-1.3 and a corrected significance value p < 0.005) in tissue obtained from smokers versus nonsmokers. Genes important for fetal growth, angiogenesis, or development of connective tissue matrix were up-regulated among smokers. The most highly up-regulated gene was CSH1, a somatomammotropin gene. Two other somatomammotropin genes (CSH2 and CSH-L1) were also up-regulated. The most highly down-regulated gene was APOBEC3A; other down-regulated genes included those that may be important in immune and barrier protection. PCR validation of the three somatomammotropin genes showed a high correlation between qPCR and microarray expression. Consequently, maternal smoking may be associated with altered gene expression in the offspring.
Effects of prenatal tobacco exposure on gene expression profiling in umbilical cord tissue.
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View SamplesWe used microarrays to detail the global program of gene expression in cytokine stimulated effector CD8 T cells.
Costimulation Endows Immunotherapeutic CD8 T Cells with IL-36 Responsiveness during Aerobic Glycolysis.
Specimen part
View SamplesDuring critical periods the developing organism is particularly sensitive to exposure to bioactive environmental contaminants. Our objective was to test p,p-DDE and dieldrin in a zebrafish whole embryo model in order to identify potential endocrine disrupting activity during development.
No associated publication
Specimen part, Treatment
View SamplesWe used a microarray to examine the global gene expression profile of MCF7 cells grown in 2D and 3D culture conditions. Our goal was to identify changes in the expression of genes that regulate iron metabolism when cellular spatial organization was altered.
Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer.
Age, Specimen part, Cell line
View SamplesThe goal of this experiment was to investigate the molecular mechanism of how Set-beta regulates neurite growth. Set-betas subcellular localization is regulated by posttranslational modifications. We found that Set-beta suppresses neurite growth of purified postnatal rat retinal ganglion cell (RGC) primary neurons when it is overexpressed in the nucleus, whereas recruiting Set-beta to cellular membrane by fusing myr-tag to its N-terminus promotes neurite growth. Here, we transfected purified by immunopanning postnatal rat RGC with wild-type Set-beta which localizes to the nucleus, myr-Set-beta which is recruited to cellular membranes, and mCherry control, and analyzed with microarrays Set-betas subcellular localization-dependent effects on gene expression. We found that wild-type Set- regulated expression of significantly more genes than myr-Set-, consistent with wild-type Set-s nuclear localization and previously described roles in regulating transcription. These data reveal potential downstream gene effectors regulating neurite growth, and specific candidate genes could be validated and tested in future experiments.
Regulating Set-β's Subcellular Localization Toggles Its Function between Inhibiting and Promoting Axon Growth and Regeneration.
Specimen part
View SamplesStrain differences in gene expression in the hypothalamus of BXD recombinant inbred mice
Sex-specific modulation of gene expression networks in murine hypothalamus.
Sex, Age, Specimen part
View SamplesThe respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cels, that work together to maintain steady-state respiration. Due to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systemically identify these subsets in human airways, by developing a schema of isolating large numbers of cells by whole lung bronchoalveolar lavage. Six subsets of phagocytic antigen presenting cells were consistently observed, which varied in their ability to internalize bacterial particles. Subsets could be further separated by their inherent capacities to upregulate CD83, CD86, and CCR7. Whole genome transcriptional profiling revealed a clade of true dendritic cells distinct from a macrophage/monocyte clade. Each clade, and each member of both clades, could be discerned by specific genes of increased expression, which would serve as markers for future studies in healthy and diseased states.
Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.
Sex, Age
View SamplesIslet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse a model for human type 1 diabetes (T1DM). The molecular events leading to insulitis are poorly understood. Since TIDM is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease.
Molecular phenotyping of immune cells from young NOD mice reveals abnormal metabolic pathways in the early induction phase of autoimmune diabetes.
Age, Specimen part
View SamplesType 1 diabetes is a multigenic disease caused by T-cell mediated destruction of the insulin producing -cells. Although conventional (targeted) approaches of identifying causative genes have advanced our knowledge of this disease, many questions remain unanswered. Using a whole molecular systems study, we unraveled the genes/molecular pathways that are altered in CD4 T-cells from young NOD mice prior to insulitis (lymphocytic infiltration into the pancreas). Many of the CD4 T-cell altered genes lie within known diabetes susceptibility regions (Idd), including several genes in the diabetes resistance region Idd13 and two genes (Khdrbs1 and Ptp4a2) in the CD4 T-cell diabetogenic activity region Idd9/11. Alterations involved apoptosis/cell proliferation and metabolic pathways (predominant at 2 weeks), inflammation and cell signaling/activation (predominant at 3 weeks), and innate and adaptive immune responses (predominant at 4 weeks). We identified several factors that may regulate these abnormalities: IRF-1, HNF4A, TP53, BCL2L1 (lies within Idd13), IFNG, IL4, IL15, and prostaglandin E2, which were common to all 3 ages; AR and IL6 to 2 and 4 weeks; and Interferon (IFN-I) and IRF-7 to 3 and 4 weeks. Others were unique to the various ages (e. g. MYC, JUN, and APP to 2 weeks; TNF, TGFB1, NFKB, ERK, and p38MAPK to 3 weeks; and IL12 and STAT4 to 4 weeks). Our data suggest that diabetes resistance genes in Idd13 and Idd9/11, and BCL2L1, IL6-AR and IFNG-IRF-1-IFN-I/IRF-7-IL12 pathways play an important role in CD4 T-cells in the early pathogenesis of autoimmune diabetes. Thus, the alternative approach of investigation at the molecular systems level has captured new information, which combined with validation studies, offers the opportunity to test hypotheses on the role played by the genes/molecular pathways identified in this study, to understand better the mechanisms of autoimmune diabetes in CD4 T-cells, and to develop new therapeutic strategies for the disease.
Molecular pathway alterations in CD4 T-cells of nonobese diabetic (NOD) mice in the preinsulitis phase of autoimmune diabetes.
Age, Specimen part
View SamplesRheumatoid arthritis (RA) is a heterogeneous disease with clinical and biological polymorphisms. However, little is known about baseline molecular variations among individual RA patients. The purpose of this study was to address this issue using F2 intercross mice generated from arthritis-prone BALB/c and arthritis-resistant DBA/1 mice deficient for interleukin 1 receptor antagonist (Il1rn). Two distinct subpopulations of arthritic mice were identified in the 38 mice studied. One subgroup of diseased mice was characterized by myeloid cell dominant inflammation, whereas the other was mainly associated with increased anti-apoptotic activities of inflammatory cells.
No associated publication
No sample metadata fields
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