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GSE107715
Mus musculus
15 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Long-term pharmacological glucocorticoid therapy causes atrophy and hypofunction of the adrenal cortex. Following glucocorticoids withdrawal, a functional and anatomic regeneration take place, whose cellular and molecular mechanisms are poorly understood
Publication Title
Sonic Hedgehog and WNT Signaling Promote Adrenal Gland Regeneration in Male Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
ACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushings disease (CD)] is the most common cause of endogenous Cushings syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, 10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also identified potential biological pathways associated with growth and invasiveness, TGF- and G protein signaling pathways, DNA damage response pathway, and pathways associated with focal adhesion. Our study revealed a differential pattern of genetic signature in a subgroup of MAC, supporting a genetic influence on corticotrophinomas in patients with CD.
Publication Title
Transcriptome Analysis Showed a Differential Signature between Invasive and Non-invasive Corticotrophinomas.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global transcriptome patterns were performed using ORE1-IOE-2h (2h after Estradiol and Mock treatment) as well as transiently (6h) overexpressed Arabidopsis mesophyll cell protoplasts
Publication Title
NAC transcription factor ORE1 and senescence-induced BIFUNCTIONAL NUCLEASE1 (BFN1) constitute a regulatory cascade in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Differentiating human dendritic cells were stimulated for 12 hours with RXR agonists (LG268, 9CRA, R- and S-9CDHRA) or agonists for RXR partners including GW3965 (LXR/ panagonist), RSG (PPAR agonist), and GW1516 (PPAR agonist) and AM580 (RARa agonist). The gene expression changes were detected globally by Affymetrix Human Genome U133 Plus 2.0 Arrays.
Publication Title
9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Increased ploidy is common in tumors but treatments for tumors with excess chromosome sets are not available. Here, we characterize high-ploidy breast cancers and identify potential anticancer compounds selective for the high-ploidy state. Among 354 human breast cancers, 10% have mean chromosome copy number exceeding 3, and this is most common in triple negative and HER2-positive types. Women with high-ploidy breast cancers have higher risk of recurrence and death in two patient cohorts, demonstrating that it represents an important group for improved treatment. Because high-ploidy cancers are aneuploid, rather than triploid or tetraploid, we devised a two-step screen to identify selective compounds. The screen was designed to assure both external validity on diverse karyotypic backgrounds and specificity for high-ploidy cell types. This screen identified novel therapies specific to high-ploidy cells. First, we discovered 8-azaguanine, an antimetabolite that is activated by hypoxanthine phosphoribosyltransferase (HPRT), suggesting an elevated gene-dosage of HPRT in high-ploidy tumors can control sensitivity to this drug. Second, we discovered a novel compound, 2,3-Diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ). DPBQ activates p53 and triggers apoptosis in a polyploid-specific manner, but does not inhibit topoisomerase or bind DNA. Mechanistic analysis demonstrates that DPBQ elicits a hypoxia gene signature and its effect is replicated, in part, by enhancing oxidative stress. Structure-function analysis defines the core benzo[g]quinoxaline-5,10 dione as being necessary for the polyploid-specific effects of DPBQ. We conclude that polyploid breast cancers represent a high-risk subgroup and that DPBQ provides a functional core to develop polyploid-selective therapy.
Publication Title
Identification of Selective Lead Compounds for Treatment of High-Ploidy Breast Cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We scored adrenocortical carcinomas and adenomas for abnormal beta-catenin staining, and sequenced the beta-catenin gene in some samples. We compared adrenocortincal carcinomas with and without abnormal beta-catenin staining and found many significant expression differences and significant results from enrichment testing. A similar comparison in the adenomas gave relatively few differences, and they did not correlate to differences found for the carcinomas. Abnormal beta-catenin staining was associated with mitotic rate and poorer patient survival in the carcinomas. In a second independent data set (given in a supplement) we again found beta-catenin associated with poor survival. The array data given is the same as GEO series GSE10927, with additional characteristics about beta-catenin, and new patient followup data. The analysis shown in a supplementary Excel file is also new.
Publication Title
Progression to adrenocortical tumorigenesis in mice and humans through insulin-like growth factor 2 and β-catenin.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 21 Downloadable Samples
Illumina HiSeq 2500
Description
Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMf, CD11cloMf are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMf and CD11cloMf increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways Overall design: CD11chiMf Sham, n=3; CD11chiMf RAS, n=4; CD11cloMf Sham, n=3; CD11cloMf RAS, n=4; KRM Sham, n=4; KRM RAS, n=3;
Publication Title
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PDE4 inhibitors, which activate cAMP signaling by reducing cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic leukemia (CLL) cells but not normal human T cells. The explanation for such differential sensitivity remains unknown. Here, we report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T and B cells.
Publication Title
Chronic lymphocytic leukemia and B and T cells differ in their response to cyclic nucleotide phosphodiesterase inhibitors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- IlluminaHiSeq2500
Description
The goal of this study is to compare the transcriptome of the 2 MVT1 subpopulations in order to identify new genes and pathways that stands beyond the CD24+ aggressive phenotype Overall design: mRNA profiles of CD24- and CD24+ cells were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500
Publication Title
Deep sequencing of mRNA in CD24(-) and CD24(+) mammary carcinoma Mvt1 cell line.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.
Publication Title
Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part
View Samples