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GSE29583
Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Though it is well established that immunological functions of CD4+ T cells are time of day-dependent, the underlying molecular mechanisms remain largely obscure. To address the question whether T cells themselves harbor a functional clock driving circadian rhythms of immune function, we analyzed clock gene expression and immune responses of CD4+ T cells purified from blood of healthy subjects at different time points throughout the day. Circadian clock function as well as immune function was further analyzed in cultivated T cells and circadian clock reporter systems. We found robust rhythms of clock gene expression as well as, after stimulation, of IFN-g production and CD40L expression in both freshly isolated and in cultured CD4+ T cells. Moreover, circadian luciferase reporter activities in CD4+ T cells and in thymic sections from PER2::LUCIFERASE reporter mice suggest that endogenous T cell clock rhythms are self-sustained under constant culture conditions. Microarray analysis of stimulated CD4+ T cell cultures revealed a rhythmic regulation of the NF-kB pathway as a candidate mechanism regulating circadian immune responses. Collectively, these data demonstrate for the first time that CD4+ T cell responses are regulated by an intrinsic cellular circadian oscillator capable of driving rhythmic adaptive immune responses in vitro and in vivo.
Publication Title
Circadian clocks in mouse and human CD4+ T cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Kaposis sarcoma (KS) is the most frequently occurring malignant tumor in patients infected with the human immunodeficiency virus. Recent studies have revealed that infection of vascular endothelial cells with Kaposi's sarcoma-associated herpes virus in vitro results in a lymphatic re-programming of these cells, with potent induction of the lymphatic marker genes podoplanin and VEGFR-3 which is mediated by upregulation of the transcription factor Prox1. However, the potential effects of Prox1 expression on the biology of KS and, in particular, on the aggressive and invasive behavior of KS tumors in vivo have remained unknown. We stably expressed Prox1 cDNA in the two mouse hemangioendothelioma cell lines EOMA and Py-4-1, well-established murine models for kaposiform hemangioendothelioma. Surprisingly, we found that expression of Prox1 was sufficient to induce a more aggressive behavior of tumors growing in syngenic mice, leading to enhanced local invasion into the muscular layer and to cellular anaplasia. This enhanced malignant phenotype was associated with upregulation of several genes involved in proteolysis, cytoskeletal reorganisation and migration. Together, these results indicate that Prox1 plays an important, previously unanticipated role in mediating the aggressive behavior of vascular neoplasms such as Kaposi's sarcoma.
Publication Title
Prox-1 promotes invasion of kaposiform hemangioendotheliomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 144 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background. Most colorectal cancers (CRC) arise in a progression through adenoma to carcinoma phenotypes as a consequence of altered genetic information. Clinical progression of CRC may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. Methodology/Principal Findings. Studies were performed on normal mucosa, adenoma, and CRC samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. RNA was isolated from 105 macro- and 40 microdissected specimens. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data were generated using two normalization algorithms: MAS5 and GCRMA with LVS. The data were evaluated using pair-wise comparisons and data decomposition into SVD modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Based on a consensus of the results obtained by two tissue handling procedures, two normalization algorithms, and two probe set sorting criteria, we identified six KEGG signaling and metabolic pathways (cell cycle, DNA replication, p53 signaling pathway, purine metabolism, pyrimidine metabolism, and RNA polymerase) that are significantly altered in both macro- and microdissected tumor samples compared to normal colon. On the other hand, pathways altered between benign and malignant tumors were identified only in the macrodissected tissues. Conclusion/Significance. Multidirectional analyses of microarray data allow the identification of essential signaling alterations underlying CRC development. Although the proposed strategy is computationally complex and laborintensive, it may reduce the number of false results.
Publication Title
Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Postmenopausal hormone therapy (HT) is associated with many diseases and conditions, but the underlying molecular mechanisms involved are incompletely understood. The aim of the current study was to investigate the effect of 4 types of HT on gene transcription. 24 women (6 women in 4 treatment groups) received 2 mg 17-estradiol combined with 1 mg noresthisterone acetate (NETA), 1 mg 17-estradiol combined with 0.5 mg NETA, tibolone, or raloxifene hydrochloride. RNA was isolated from whole blood before treatment (baseline) and after 6 weeks on treatment. The changes in mRNA from baseline to 6 weeks were assessed with a microarray chip.
Publication Title
A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of the present study was to examine potential differences in the regulation of myocardial ECM constituents, in mice that develop hypertrophy only (ABnonHF) and in mice that develop overt heart failure (ABHF) as response to pressure overload.
Publication Title
Differential regulation of extracellular matrix constituents in myocardial remodeling with and without heart failure following pressure overload.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
To identify the downstream molecules that mediate PIM1 induced aggressive prostate cancer cells, p53 and Rb-deficient mouse prostate epithelial cells were transduced with PIM1 lentivirus and performed a gene expression profile microarray.
Publication Title
Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM Kinase.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute Myeloid Leukemia (AML) is a heterogeneous disease from the molecular and biological standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients that shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, while the rest presented with silencing of this gene and co-expression of certain T cell markers. DNA methylation studies revealed that these two groups of patients could be readily segregated in an unsupervised fashion based on their DNA methylation profiles alone. Furthermore, CEBPA silencing was associated with the presence of an aberrant DNA hypermethylation signature, which was not present in the CEBPA mutant group. This aberrant hypermethylation occurred more frequently at sites within CpG islands. CEBPA silenced leukemias also displayed marked hypermethylation when compared with normal CD34+ hematopoietic cells, while CEBPA mutant cases showed only mild changes in DNA methylation when compared to these normal progenitors. Biologically, CEBPA silenced leukemias presented with a decreased response to myeloid growth factors in vitro.
Publication Title
Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
LPL co-deregulated genes after LPL specific siRNA knock-down
Publication Title
Lipoprotein lipase in chronic lymphocytic leukaemia - strong biomarker with lack of functional significance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in KIT or PDGFRA of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations.
Publication Title
Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression.
Sample Metadata Fields
Sex, Specimen part, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Renal recovery following injury relies on cellular regeneration. In the mouse kidney following injury, injured epithelial cells undergoes de-differentiate, proliferate and re-differentiate into functional cells, following a a tightly controlled genetic programme where specific sets of genes are up-regulated.
Publication Title
Histone deacetylase inhibitor enhances recovery after AKI.
Sample Metadata Fields
Specimen part
View Samples