Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognizable by its distinctive red skin lesions. The lesions are KSHV infected spindle cells, most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. Here we examine KSHVs modulation of Notch signaling using wild-type LEC cells co-cultured with DLL4 and JAG1 expressing LEC cells.
KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia.
No sample metadata fields
View Sampleseffect of overexpression of GATA-6 in P19 CL6 induced cells
Wnt2 is a direct downstream target of GATA6 during early cardiogenesis.
Cell line
View SamplesOvarian cancer patients are generally diagnosed at stage III/IV, when ascites is common. The volume of ascites positively correlates with the extent of metastasis and negatively with prognosis. Membrane GRP78, a stress-inducible endoplasmic reticulum chaperone which also appears on the plasma membrane (memGRP78) of aggressive cancers, plays a crucial role in the maintenance of embryonic stem cells. Our present study demonstrates that tumor cells isolated from ascites generated by epithelial ovarian cancer (ID8 cells) bearing mice have increased memGRP78 expression compared to ID8 cells in normal culture. We hypothesize that these ascites associated memGRP78+ cells are cancer stem-like cells (CSC) and memGRP78 is functionally important in CSCs. Supporting this hypothesis, we show that memGRP78+ cells isolated from ascites have increased sphere forming and tumor initiating abilities compared to memGRP78- cells. When the tumor microenvironment is recapitulated by adding ascites fluid to cell culture, ID8 cells express more memGRP78 and increased self-renewing ability compared to those cultured in medium alone. Moreover, compared to their counterparts cultured in normal medium, ID8 cells cultured in ascites, or isolated from ascites, show an increased expression of stem cell markers Sca-1, Snail and SOX9. Importantly, antibodies directed against the carboxy (COOH)-terminal domain of GRP78 significantly reduce the self-renewing ability of murine and human ovarian cancer cells pre-incubated with ascites, associated with a decreased phosphorylation of Akt and GSK3, and reduced level of the transcriptional factor Snail. Based on this data, we suggest that memGRP78 is a logical therapeutic target for late stage ovarian cancer.
Syngeneic Murine Ovarian Cancer Model Reveals That Ascites Enriches for Ovarian Cancer Stem-Like Cells Expressing Membrane GRP78.
Disease
View Samples[original title] LMP-420: a novel purine nucleoside analogue with potent cytotoxic effects for chronic lymphocytic leukemia cells and minimal toxicity for normal hematopoietic cells.
LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells.
No sample metadata fields
View SamplesTotal RNA samples from Vax2 knockout mouse eyes (at least two biological replicates) were profiled by gene expression. As control we used total RNA from wild type eyes. The analysis was carried out at five different developmental stages: E10.5, E12.5, E16.5, P8, and P60.
Vax2 regulates retinoic acid distribution and cone opsin expression in the vertebrate eye.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Specimen part
View SamplesIn this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesIn this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesIn this study we identified that Sirt1 is important for mouse trophoblast stem cell (TSC) differentiation. The transcriptome of wild-type and Sirt1-null TSC were analyzed to identify dysregulation of signaling pathways.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesThe 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.
NCBP2 modulates neurodevelopmental defects of the 3q29 deletion in Drosophila and Xenopus laevis models.
Specimen part, Subject
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