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GSE34569
Sus scrofa
19 Downloadable Samples
Affymetrix Porcine Genome Array (porcine)
Description
The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI.
Publication Title
Identification of temporal and region-specific myocardial gene expression patterns in response to infarction in swine.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaHiSeq2500
Description
We report on two novel t(15;21) alterations [t(15;21)(q24;q22) and t(15;21)(q21;q22)], which led to concurrent disruption of RUNX1 and two translocation partner genes encoding for transcription factors (SIN3A, TCF12) Overall design: Examination of four different patients with myeloid disorders. 2 out of 4 have been analyzed by means RNAseq
Publication Title
t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
- NextSeq 500
Description
The SWI/SNF-family chromatin remodeling protein ATRX is a tumor suppressor in sarcomas, gliomas and other malignancies. Its loss of function facilitates the alternative lengthening of telomeres (ALT) pathway in tumor cells, while it also affects Polycomb repressive complex 2 (PRC2) silencing of its target genes. To further define the role of inactivating ATRX mutations in carcinogenesis, we knocked out atrx in our previously published p53/nf1-deficient zebrafish line that develops malignant peripheral nerve sheath tumors and gliomas. Complete inactivation of atrx using CRISPR-cas9 was lethal in developing fish and resulted in an alpha-thalassemia-like phenotype including reduced alpha-globin expression. In p53/nf1-deficient zebrafish neither peripheral nerve sheath tumors nor gliomas showed accelerated onset in atrx+/- fish, but these fish developed various tumors that were not observed in their atrx+/+ siblings, including epithelioid sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma and rare types of carcinoma. Most of these cancer types are included in the AACR Genie database of human tumors associated with mutant ATRX, indicating that our zebrafish model reliably reflects a role for ATRX-loss in the early pathogenesis of these types of human cancers. RNA-seq of p53/nf1- and p53/nf1/atrx-deficient tumors revealed that down-regulation of telomerase accompanied ALT-mediated lengthening of the telomeres in atrx-mutant samples. Moreover, inactivating mutations in atrx disturbed PRC2-target gene silencing, indicating a connection between ATRX loss and PRC2 dysfunction in cancer development. Overall design: Gene expression values were derived from paired end RNA-Seq data that compared zebrafish samples from p53/nf1/atrx-deficient tumors to samples from atrx-wildtype controls (3 vs. 3 samples).
Publication Title
Loss of atrx cooperates with p53-deficiency to promote the development of sarcomas and other malignancies.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background & Aims: Chronic hepatitis C virus (HCV) infection is complicated by hepatic fibrosis. Hypothesizing that fibrogenic signals may originate in cells susceptible to HCV infection, gene expression of hepatocytes was analyzed from persons with chronic HCV at different stages of liver fibrosis. Methods: HCV-infected subjects with significant liver fibrosis (Ishak fibrosis 3) were matched for age, race, and gender to subjects with minimal fibrosis (Ishak fibrosis 0-1). RNA from portal tracts and hepatic parenchyma was isolated from biopsies by laser capture and transcriptome profiling was performed using hybridization arrays. Results: Portal tracts from both groups were enriched for immune related genes when compared to hepatocytes but high fibrosis subjects showed a loss of this enrichment. Hepatocytes from persons with high fibrosis were depleted for genes involved in small molecule and drug metabolism, especially butyrylcholinesterase (BCHE), a gene involved in the metabolism of drugs of abuse. Differential expression of BCHE was validated in the same tissues using qPCR. Cross-sectional and longitudinal testing in an expanded cohort of HCV-infected individuals showed that serum BCHE activity decreased in advance of progression to fibrosis. Conclusion: Chronic HCV infection is associated with a loss of hepatocyte metabolic function, decreased enrichment of immune-related genes in portal tracts and downregulation of BCHE in hepatocytes. Our results indicate that BCHE may be involved in the progression of fibrosis during HCV infection among injection drug users and may serve as a useful marker for fibrosis progression.
Publication Title
Laser captured hepatocytes show association of butyrylcholinesterase gene loss and fibrosis progression in hepatitis C-infected drug users.
Sample Metadata Fields
Sex, Age, Race
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
How cells acquire their fate is a fundamental question in both developmental and regenerative biology. Multipotent progenitors undergo gradual cell fate restriction in response to temporal and positional cues from the microenvironment, the nature of which is far from being clear. In the case of the lymphatic system, venous endothelial cells are thought to give rise to lymphatic vessels, through a process of trans-differentiation. Upon expression of a set of transcription factors, venous cells acquire a lymphatic fate, and bud out to generate the lymphatic vasculature. In this work we challenge this view and show that while lymphatic endothelial cells (LECs) do arise in the Cardinal Vein (CV), they do so from a previously uncharacterized pool of multipotent angioblasts. Using lymphatic-specific transgenic zebrafish, in combination with endothelial photoconvertible reporters, and long-term live imaging, we demonstrate that these multipotent angioblasts can generate not only lymphatic, but also arterious, and venous fates. We further reveal that the underlying endoderm serves as a source of Wnt5b, which acts as a lymphatic inductive signal, promoting the angioblast-to-lymphatic transition. Moreover, Wnt5b induced lymphatic specification in human embryonic stem cells- derived vascular progenitors, suggesting that this process is evolutionary conserved. Our results uncover a novel mechanism of lymphatic vessel formation, whereby multipotent angioblasts and not venous endothelial cells give rise to the lymphatic endothelium, and provide the first characterization of their inductive niche. More broadly, our findings highlight the CV as a plastic and heterogeneous structure containing different cell populations, analogous to the hematopoietic niche in the aortic floor. Overall design: Following Kaede photoconversion of dorsal or ventral halves of the PCV in Tg(fli1:gal4;uasKaede) embryos at 24 hpf, 6Â embryos per group were used for FACS isolation of Kaede photconverted (red) ECs.
Publication Title
Lymphatic vessels arise from specialized angioblasts within a venous niche.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NOTCH proteins regulate signaling pathways involved in cellular differentiation, proliferation and death. Overactive Notch signaling as been observed in numerous cancers and has been extensively studied in the context of T-cell acute lymphoblastic leukemia (T-ALL) where more than 50% of pateints harbour mutant NOTCH1. Small molecule modulators of these proteins would be important for understanding the role of NOTCH proteins in malignant and normal biological processes.
Publication Title
Direct inhibition of the NOTCH transcription factor complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Expression of a constitutively active Notch-1 intracellular domain (NICD) in MCF-10A cells was found to induce two distinct types of 3D structures: large, hyperproliferative structures and small, growth-arrested structures with reduced cell-to-matrix adhesion. These heterogeneous phenotypes reflect differences in Notch pathway activation levels. High Notch activity caused loss of cell adhesion and inhibition of proliferation, whereas low Notch activity maintained matrix adhesion and provoked a strong hyperproliferative response. In order to gain insight into the dosage-dependent transcriptional events triggered by Notch1 activation, gene expression profiles induced 48 hours after infection of MCF-10A cells with retroviral vectors expressing full-length Notch-1, L1601P+P, or NICD were compared. Full-length Notch-1 induced the weakest effect, L1601P+P induced an intermediate effect and NICD induced the strongest effect. Results provide insight into the dichotomous activites of Notch during development and tumorigenesis.
Publication Title
Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Platelets are a rich source of many cytokines and chemokines including transforming growth factor -1 (TGF1). TGF1 is required to convert conventional CD4+ T (Tconv) cells into induced regulatory T (iTreg) cells that express the transcription factor Foxp3. To explore whether other platelet contents will affect the properties of TGF induced Treg cell, we used platelet lysate that contain many other cytokines and chemokines besides TGF1 (pltTGF) to induce Foxp3 expression (pltTGFb-iTreg) from conventional CD4+ T (Tconv) cells. We used purified TGF1 to induce Treg (purTGF-iTreg) cells as a control. Gene expression profiles in iTreg cells were analyzed by microarray asay.
Publication Title
TGF-β1 along with other platelet contents augments Treg cells to suppress anti-FVIII immune responses in hemophilia A mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Despite initial and often dramatic responses of epidermal growth factor receptor (EGFR)-addicted lung tumors to the EGFR-specific tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, nearly all develop resistance and relapse. To explore novel mechanisms mediating acquired resistance, we employed non-small-cell lung cancer (NSCLC) cell lines bearing activating mutations in EGFR and rendered them resistant to EGFR-specific TKIs through chronic adaptation in tissue culture. In addition to previously observed resistance mechanisms including EGFR-T790M ''gate-keeper'' mutations and MET amplification, a subset of the seven chronically adapted NSCLC cell lines including HCC4006, HCC2279 and H1650 cells exhibited marked induction of fibroblast growth factor (FGF) 2 and FGF receptor 1 (FGFR1) mRNA and protein. Also, adaptation to EGFR-specific TKIs was accompanied by an epithelial to mesenchymal transition (EMT) as assessed by changes in CDH1, VIM, ZEB1 and ZEB2 expression and altered growth properties in Matrigel. In adapted cell lines exhibiting increased FGF2 and FGFR1 expression, measures of growth and signaling, but not EMT, were blocked by FGFR-specific TKIs, an FGF-ligand trap and FGFR1 silencing with RNAi. In parental HCC4006 cells, cell growth was strongly inhibited by gefitinib, although drug-resistant clones progress within 10 days. Combined treatment with gefitinib and AZD4547, an FGFR-specific TKI, prevented the outgrowth of drug-resistant clones. Thus, induction of FGF2 and FGFR1 following chronic adaptation to EGFR-specific TKIs provides a novel autocrine receptor tyrosine kinase-driven bypass pathway in a subset of lung cancer cell lines that are initially sensitive to EGFR-specific TKIs. The findings support FGFR-specific TKIs as potentially valuable additions to existing targeted therapeutic strategies with EGFR-specific TKIs to prevent or delay acquired resistance in EGFR-driven NSCLC. Overall design: Examination of mRNA levels in DMSO and gefitinib-resistant cultures of HCC4006 and HCC827. Each group has two replicates.
Publication Title
A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Although transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/ orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA binding protein Tcf-1, a T-cell specific mediator of Wnt signaling. Yet the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate. We show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of Tcell determination for progression beyond the early thymic progenitor (ETP) stage. The global expression profile of Tcf-1 deficient progenitors indicates that basic processes of DNA metabolism are downregulated in its absence and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the roadmap of T-cell development.
Publication Title
T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling.
Sample Metadata Fields
Specimen part
View Samples