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GSE42913
Homo sapiens
31 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Resistance formation is one of the major hurdles in cancer therapy. Metronomic anti-angiogenic treatment of xenografted prostate cancer tumors in SCID mice with cyclophosphamide (CPA) results in the appearance of resistant tumors. To investigate the complex molecular changes occurring during resistance formation, we performed a comprehensive gene expression analysis of the resistant tumors in vivo. We observed a multitude of differentially expressed genes, e.g., PASD1, ANXA3, NTS or PLAT, when comparing resistant to in vivo passaged tumor samples. Furthermore, tumor cells from in vivo and in vitro conditions showed a significant difference in target gene expression. We assigned the differentially expressed genes to functional pathways like axon guidance, steroid biosynthesis and complement and coagulation cascades. Most of the genes were involved in anti-coagulation, indicating its possible importance. Upregulation of anti-coagulatory ANXA3 and PLAT and downregulation of PLAT inhibitor SERPINA were validated by qPCR. In contrast, coagulation factor F3 was upregulated, accompanied by the expression of an altered gene product. These findings give insights into the resistance mechanisms of metronomical CPA treatment suggesting an important role of anti-coagulation in resistance formation.
Publication Title
A Comprehensive Gene Expression Analysis of Resistance Formation upon Metronomic Cyclophosphamide Therapy.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Drosophila melanogaster
- 66 Downloadable Samples
Illumina HiSeq 2000
Description
The 1.6 Mbp deletion on chromosome 3q29 is associated with a range of neurodevelopmental disorders, including schizophrenia, autism, microcephaly, and intellectual disability. Despite its importance towards neurodevelopment, the role of individual genes, genetic interactions, and disrupted biological mechanisms underlying the deletion have not been thoroughly characterized. Here, we used quantitative methods to assay Drosophila melanogaster and Xenopus laevis models with tissue-specific individual and pairwise knockdown of 14 homologs of genes within the 3q29 region. We identified developmental, cellular, and neuronal phenotypes for multiple homologs of 3q29 genes, potentially due to altered apoptosis and cell cycle mechanisms during development. Using the fly eye, we screened for 314 pairwise knockdowns of homologs of 3q29 genes and identified 44 interactions between pairs of homologs and 34 interactions with other neurodevelopmental genes. Interestingly, NCBP2 homologs in Drosophila (Cbp20) and X. laevis (ncbp2) enhanced the phenotypes of homologs of the other 3q29 genes, leading to significant increases in apoptosis that disrupted cellular organization and brain morphology. These cellular and neuronal defects were rescued with overexpression of the apoptosis inhibitors Diap1 and xiap in both models, suggesting that apoptosis is one of several potential biological mechanisms disrupted by the deletion. NCBP2 was also highly connected to other 3q29 genes in a human brain-specific interaction network, providing support for the relevance of our results towards the human deletion. Overall, our study suggests that NCBP2-mediated genetic interactions within the 3q29 region disrupt apoptosis and cell cycle mechanisms during development. Overall design: mRNA-sequencing of Drosophila neuron-specific RNAi knockdown (whole head) for four individual 3q29 homologs (DLG1, NCBP2, FBXO45, and PAK2), two pairwise knockdowns of 3q29 homologs (NCBP2/DLG1 and NCBP2/FBXO45), and two VDRC wild-type controls (GD and KK backgrounds). Sequencing was performed using Illumina HiSeq 2000 on three biological replicates per sample, with two-three technical replicates per biological replicate.
Publication Title
NCBP2 modulates neurodevelopmental defects of the 3q29 deletion in Drosophila and Xenopus laevis models.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Male Wistar rats weighing 90-120 g were acclimatized for one week and fed standard laboratory chow, at which time the animals were divided into two groups. Animals were then pair-fed for 8 weeks a regular laboratory chow and water ad libitum or Lieber-DeCarli diet (36% calories from ethanol). Control animals received the iso-caloric amount of dextrose to replace ethanol. After 8 weeks of differential feeding rats were euthanized, the pancreas immediately dissected and stored at -80?C until RNA isolation. RNA expression was analyzed using Affymetrix RAE230A gene chips
Publication Title
Long-term ethanol consumption alters pancreatic gene expression in rats: a possible connection to pancreatic injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 63 Downloadable Samples
- Illumina HiSeq 2000
Description
As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identify a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. We test 565 pairwise knockdowns in the developing eye, and identify 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppress or enhance cell proliferation phenotypes compared to one-hit knockdowns. These interactions within cell proliferation pathways are also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for pervasive genetic interactions within CNVs towards cellular and developmental phenotypes. Overall design: mRNA-sequencing of Drosophila neuron-specific knockdown model heads for six 16p11.2 homologs and wild-type control. Sequencing was performed using Illumina HiSeq 2000 on three biological replicates per sample, with three technical replicates per biological replicate.
Publication Title
Pervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Arabidopsis thaliana
- 40 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Common and distinct transcriptomic responses to moderate light and drought stress in the different mutants.
Publication Title
Decreasing electron flux through the cytochrome and/or alternative respiratory pathways triggers common and distinct cellular responses dependent on growth conditions.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The translocase of the inner membrane 17-1 (Tim17-1) plays a defined role in germination in Arabidopsis thaliana
Publication Title
The mitochondrial protein import component, TRANSLOCASE OF THE INNER MEMBRANE17-1, plays a role in defining the timing of germination in Arabidopsis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Expression of insulin in terminally differentiated non-beta pancreatic cell types could be important for treating type-1 diabetes. We observed that the kinase inhibitor GW8510 up-regulated insulin expression in mouse pancreatic alpha cells.
Publication Title
GW8510 increases insulin expression in pancreatic alpha cells through activation of p53 transcriptional activity.
Sample Metadata Fields
Cell line, Compound
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Arabidopsis MPK4 is involved in the control of antagonism between salicylic acid (SA) and ethylene (ET)/jasmonic acid (JA) pathways in the plant innate immune system as a repressor of the SA pathway, but an activator of the ET/JA pathway. Here we and use comparative microarray analysis of ctr1, ctr1/mpk4, mpk4 and wild type to show that MPK4 is required for only a narrow subset of ET regulated genes.
Publication Title
Arabidopsis systemic immunity uses conserved defense signaling pathways and is mediated by jasmonates.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy.
Publication Title
IL-17/Th17 pathway is activated in acne lesions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1500
Description
Transcriptomal comparison between group 2 innate lymphoid cells (ILC2s) in the murine small intestine (SI-ILC2s) and those in white adipose tissue (WAT-ILC2s). Overall design: mRNA profiles of group 2 innate lymphoid cells (ILC2s) sort-purified from small intestinal lamina propria and mesenteric white adipose tissue of 9-week-old wild type (WT) mice were generated by sequencing, in duplicate, using Illumina HiSeq1500.
Publication Title
Innate Lymphoid Cells in the Induction of Obesity.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples