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GSE45857
Bos taurus
27 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Female sex steroid hormones, estradiol-17 (E2) and progesterone (P4) regulate reproductive function and gene expression in a broad range of tissues. Given the central role of the liver in regulating homeostasis including steroid hormone metabolism, we sought to understand how E2-17 and P4 interact to affect global gene expression in liver. Eight ovariectomized cows were randomly assigned to 4 treatment groups applied in a replicated Latin Square design: 1) No hormone supplementation, 2) E2-17 treatment (ear implant), 3) P4 treatment (intravaginal inserts), and 4) E2-17 combined with P4. After 14 d of treatment, liver biopsies were collected, allowing 28 d intervals between periods. Changes in gene expression in the liver biopsies were monitored using Affymetrix bovine-specific arrays. Treatment with E2-17 altered expression of 479 genes, P4 472 genes, and combined treatment significantly altered expression of 468 genes. In total, 578 genes exhibited altered expression including a remarkable number (346 genes) that responded similarly to E2-17, P4, or combined treatment. Additional evidence for similar gene expression effects of E2-17 and/or P4 were: principal component analysis placed almost every treatment array at a substantial distance from control arrays; Venn diagrams indicated overall treatment effects for most regulated genes; clustering analysis indicated the two major clusters had all treatments upregulating (cluster 1; 172 genes) or downregulating (cluster 2: 173 genes) expression. Thus, unexpectedly, common biological pathways are regulated by E2-17 and/or P4 in liver. Future studies are needed to elucidate mechanism(s) responsible for overlapping actions of E2-17 and P4 on the liver transcriptome. KEYWORDS: estradiol, progesterone, global gene expression, liver, cows.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 103 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 131 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Lung cancers are a heterogeneous group of diseases with respect to biology and clinical behavior. Currently, diagnosis and classification are based on histological morphology and immunohistological methods for discrimination between two main histologic groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) which account for 20% and 80% of lung carcinomas, respectively. NSCLCs, which are divided into the three major subtypes adenocarcinoma, squamous cell carcinoma and dedifferentiated large cell carcinoma, show different characteristics such as the expression of certain keratins or production of mucin and lack of neuroedocrine differentiation. The molecular pathogenesis of lung cancer involves the accumulation of genetic und epigenetic alterations including the activation of proto-oncogenes and inactivation of tumor suppressor genes which are different for lung cancer subgroups. The development of microarray technologies opened up the possibility to quantify the expression of a large number of genes simultaneously in a given sample. There are several recent reports on expression profiling on lung cancers but the analysis interpretation of the results might be difficult because of the heterogeneity of cellular components. The methods used for sample selection and processing can have a strong influence on the expression values obtained through microarray profiling. Laser capture microdissection (LCM) provides higher specificity in the selection of target cells compared to traditional bulk tissue selection methods, but at an increased processing cost.
Publication Title
Lung cancer transcriptomes refined with laser capture microdissection.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 103 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Marked expression differences in intraclonal fractions suggest potential pathological and therapeutic relevance of studying intraclonal CLL fractions as compared to bulk cells.
Publication Title
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 115 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The presence of Donor-Specific anti-HLA Antibodies (DSA) is associated with an increased risk of both acute and chronic antibody-mediated rejection (AMR) in kidney allografts. AMR has remained challenging in kidney transplantation and is the major cause of late allograft loss. However, not all patients with DSA develop AMR, leading to the question of whether this represents accommodation, if other protective mechanisms exist or if this is actually a state of pre-rejection.
Publication Title
A pathogenesis-based transcript signature in donor-specific antibody-positive kidney transplant patients with normal biopsies.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 94 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to characterize the whole blood global gene expression profiles in 98 children with P. falciparum cerebral malaria
Publication Title
Activated Neutrophils Are Associated with Pediatric Cerebral Malaria Vasculopathy in Malawian Children.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 90 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays. Immunohistochemistry for C4d was performed on paraffin-embedded sections. Of the 255 biopsies analyzed, 51% were C4d negative, 4% were minimal, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+. Minimal and focal/ diffuse PTC C4d+ staining were associated with a higher frequency of donor-specific anti-HLA antibodies (DSA) (67% vs. 82% vs. 25%), antibody mediated rejection (AMR) (66% vs. 89% vs. 19%) and mean glomerulitis (0.88 vs. 0.65 vs. 0.25, p=0.003), interstitial inflammation (1.25 vs. 1.41 vs. 0.79; p=0.003) and peritubular capillaritis scores (1.5 vs. 1.5 vs. 0.34; p < 0.001), compared to the C4d negative group, respectively. There were no differences in the DSA frequency, AMR rate, and Banff scores between isolated glomerular C4d+ and negative patients. While both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, and interferon-gamma and rejection induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis based transcripts, there was no activation of immune-response related genes in isolated glomerular C4d+ biopsies. In summary, minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mantle Cell Lymphoma (MCL) is a mostly incurable malignancy arising from nave B cells (NBC) in the mantle zone of lymph node follicles. We analyzed genome-wide methylation in MCL patients using the HELP (Hpa II tiny fragment Enrichment by Ligation mediated PCR) assay and found significant aberrancy in promoter methylation patterns as compared to normal NBCs. Using biological and stringent statistical criteria, we further identified four hypermethylated genes CDKN2B, MLF-1, PCDH8, HOXD8 and four hypomethylated genes CD37, HDAC1, NOTCH1 and CDK5 where aberrant methylation was associated with inverse changes in mRNA levels. MassArray Epityper analysis confirmed the presence of differential methylation at the promoter region of these genes. Immunohistochemical analysis of an independent cohort of 14 MCL patient samples, confirmed CD37 surface expression in 93% of patients, validating its selection as a target for MCL therapy. Treatment of MCL cell lines with a novel small modular immunopharmaceutical(CD37-SMIP) resulted in significant loss of viability in cell lines with intense surface CD37 expression. Treatment of MCL cell lines with the DNA methyltransferase inhibitor decitabine resulted in reversal of aberrant hypermethylation and synergized with the HDAC inhibitor SAHA in induction of the four hypermethylated genes CDKN2B, MLF-1, PCDH8 and HOXD8. The combination of Decitabine and SAHA also resulted in potent and synergistic anti-MCL cytotoxicity as compared to either drug alone. In conclusion, our analysis shows prominent and aberrant methylation of the MCL genome and identifies novel differentially methylated and expressed genes in MCL cell lines and patient samples. Furthermore, our data suggest that differentially methylated genes can be targeted for therapeutic benefit in MCL.
Publication Title
Genomewide DNA methylation analysis reveals novel targets for drug development in mantle cell lymphoma.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We investigated the clinical, histopathologic and genomic features of donor-specific antibody (DSA) +/C4d- and DSA-/C4d- transplant glomerulopathy (TGP) using microarrays. Comparison of the gene expression profiles of DSA-/C4d- TGP biopsies with ptc+g score > 1 to normal and IFTA (Interstitial Fibrosis and Tubular Atrophy) biopsies by microarrays revealed increased expression of quantitative cytotoxic T cell--associated transcripts (QCAT). However, CAMR (chronic antibody-mediated rejection) and DSA+/C4d- TGP had increased expression of QCAT, interferon-gamma and rejection induced, constitutive macrophage-associated, natural killer cell-associated, and DSA selective transcripts. B cell and endothelial cell associated transcripts expression were upregulated only in CAMR biopsies. Our results suggest that while DSA+/C4d- TGP should be classified under CAMR, DSA-/C4d- TGP with ptc+g score > 1 probably develops through a chronic cellular immune response.
Publication Title
The clinical and genomic significance of donor-specific antibody-positive/C4d-negative and donor-specific antibody-negative/C4d-negative transplant glomerulopathy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We study the global gene expression profiles of BKV viremia and nephropathy patients using microarrays in order to better understand the immunologic response to polyomavirus BK (BKV).
Publication Title
Genomics of BK viremia in kidney transplant recipients.
Sample Metadata Fields
Specimen part, Disease
View Samples