Our overall objective is to identify key differences in gene expression signaling pathways in the epithelial and intralobular stromal compartments during prepartum mammary remodeling and development in the dry cow.
Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows.
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Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Age, Specimen part, Treatment
View SamplesMethionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Age, Specimen part
View SamplesClinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.
Specimen part
View SamplesRNA from two murine mesothelioma cell lines (AC29 and AB1) was extracted and hybridized to Affymetrix Microarrays to compare gene expression. Both mesothelioma cell lines were established following intraperitoneal introduction of crocidolite (asbestos) fibers (Davis et al. 1992) in CBA mice (AC29 cell line), and BALB/c mice (AB1).
Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy.
Sex
View SamplesIL-22 acts on epithelial cells and has been shown to induce tissue protective and wound healing responses in these cells. But it has recently been decribed that IL-22 exacerbates ileatis after infection with T. gondii.
Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.
Specimen part, Time
View SamplesChronic Lymphocytic Leukemia (CLL) cells multiply in secondary lymphoid tissue but the mechanisms leading to their proliferation are still uncertain. In addition to BCR-triggered signals, other microenvironmental factors might well be involved. In proliferation centres, leukemic B cells are in close contact with CD4+CD40L+T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an IL-21-induced gene signature in CLL, containing components of JAK-STAT and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 productionex vivoby LN CD4+CXCR5+ follicular helper T cells. These results indicate that, in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL.
IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells.
Specimen part, Treatment
View SamplesRegulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we have compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Among these CD4+ T cell subsets, we detected differential expression of 421 proteins and 640 mRNAs, with only 48 molecules shared. Fifty proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFkB-, PI3 kinase/mTOR-, NFAT- and STAT pathways and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFkB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, while transitional FOXP3+ cells can. Our collective data reveal that Tregs protect their identity by a unique “wiring” of signalling pathways Overall design: mRNA profiles of 5 CD4+ T cell populations were generated by deep sequencing, in triplicate
Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity.
Subject
View Samplesexpression profiles kPSCs versus cMSC
The human kidney capsule contains a functionally distinct mesenchymal stromal cell population.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA-Seq provides new insights in the transcriptome responses induced by the carcinogen benzo[a]pyrene.
Cell line, Compound, Time
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