Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative. Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype. We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients.
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
Cell line
View SamplesWe report the application of low cell number sequencing of identifiable Drosophila melanogaster neurons following behavior. We demonstate the feasibility of identifying the transcriptome of 5 Mushroom Body output Neurons and 2 classes of Kenyon Cells. We find these neurons display a diverse repertoire of receptors and signaling transcripts. This information alone seems to be enough to identify each class of neurons in the study. In additional we show that aversive long-term memory induces changes in gene transcript levels in a subset of these neurons. This study provides a framework for identifying neuronal classes in Drosophila melanogaster and gaining insight into the interplay between behavior and gene regulation. Overall design: 5 Mushroom Body output neurons and 2 classes of kenyon cells are used to look at general gene expression and changes following aversive long term memory. Paired control and trained animals were used and a minimum of 4 pairs up to 6 pairs. Animals were of the same background (w1118). Animals were aged and parental matched. Cells were harvested at the same chronological time for the animals across all experiments. All animals were exposed to 1 minute of each odor and 1 minute of a series of 12 5second 60V shocks. This was considered one block and then the animals had spaced training of each block so there was a 10 minute break between 8 blocks of training. Trained animals had an odor paired with a shock, control animals received the shock then the odor stimulus. All cells were harvested usign a patch pipet from living animals on an electrophysiology rig within a half hour of the end of training. Cells were amplified using the Clontech SMARTer Ultra Low Input RNA version 2 High Volume kit. 2 Brain samples were also collected and 3-4 whole fly samples for each genotype were collected to account for background differences across flies.
Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression.
Subject
View SamplesRNA-seq analysis documented mRNA changes in total pancreatic RNA preparations 14 days after Ptf1a inactivation. Overall design: pancreas mRNA profiles of Tamoxifen treated adult control mice [Ptf1a(CreER/+)] and Ptf1a conditional knockout mice [Ptf1a(CreER/fl)] were generated by deep sequencing using an Illumina Hiseq 2500.
The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma.
No sample metadata fields
View SamplesDysfunction in type I interferon (IFN) signaling occurs in patients with stage II or more advanced cancer. After screening the effects of a panel of 12 melanoma cell lines on PBMCs of healthy volunteers of IFNalpha signal pathway, two groups of melanoma cell lines could be identified one with stronger suppression (low pSTAT-1 group) than the other (high pSTAT-1 group). Comparative global gene expression between two groups identified 6771 differential expression genes. This gene list indicated down regulation of IFNalpha signal in immune suppressive melanoma cells. To evaluate this gene list for predictive power on IFNalpha signal modulatory function, we analyzed gene expression 41 independent melanoma cell lines and heat map clusters these cell lines into two groups, one with strong immune suppressive function and other with less effect.
Melanoma NOS1 expression promotes dysfunctional IFN signaling.
Disease, Disease stage, Cell line
View SamplesBcl11a is a transcription factor known to regulate lymphoid and erythroid development. Recent bioinformatic analysis of global gene expression patterns has suggested a role for Bcl11a in the development of dendritic cell (DC) lineages. We tested this hypothesis by analyzing the development of DC and other lineages in Bcl11a(-/-) mice. We show that Bcl11a is required for expression of IL-7 receptor (IL-7R) and Flt3 in early hematopoietic progenitor cells. The loss of IL-7R(+) common lymphoid progenitors accounts for previously described lymphoid defects in Bcl11a(-/-) mice. In addition, we found severely decreased numbers of plasmacytoid dendritic cells (pDCs) in Bcl11a(-/-) fetal livers and in the bone marrow of Bcl11a(-/-) fetal liver chimeras. Moreover, Bcl11a(-/-) cells show severely impaired in vitro development of Flt3L-derived pDCs and classical DCs (cDCs). In contrast, we found normal in vitro development of DCs from Bcl11a(-/-) fetal liver cells treated with GM-CSF. These results suggest that the persistent cDC development observed in Bcl11a(-/-) fetal liver chimeras reflects derivation from a Bcl11a- and Flt3-independent pathway in vivo.
Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo.
Specimen part
View SamplesThe present study reveals LMYC and MXD1 as novel regulators of a transcriptional program that is modulated during the maturation of Batf3-dependent dendritic cells (also known as type I classical dendritic cells or cDC1s).
The MYCL and MXD1 transcription factors regulate the fitness of murine dendritic cells.
Specimen part
View SamplesProfiling of MCF-7 cell lines stably overexpressing constitutively active Raf-1, constitutively active MEK, constitutively active c-erbB-2, or ligand-activatable EGFR as models of overexpressed growth factor signaling, as well as control vector transfected cells (coMCF-7) and control vector transfected cells long-term adapted for estrogen-independent growth (coMCF-7/lt-E2).
Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors.
Cell line
View SamplesES cells differentiated in the presence of the Wnt inhibitor DKK1 fail to express the transcription factor Snail and undergo EMT or mesoderm differentiation. We generated an ES cell line, A2.snail, that induced Snail expression upon addition of doxycycline addition.
Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.
Specimen part, Cell line
View SamplesWe tested the hypothesis that a set of differentially expressed genes could be used to predict cardiovascular phenotype in mice after prolonged catecholamine stress.
Gene expression profiling: classification of mice with left ventricle systolic dysfunction using microarray analysis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages.
Specimen part
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