The goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint.
Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake.
Sex, Specimen part
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Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease
View SamplesAttempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NF-kappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease
View SamplesComparison of gene expression profiling analysis of bone marrow isolated CD34+ cells from patients with MALT lymphoma vs. healthy individuals revealed a large number of differentially expressed genes that included NF-kB target genes, genes involved in inflamatory signalling and immunoglobulin genes, suggesting an early lymphoid B-cell priming.
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease, Disease stage
View SamplesAttempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NFkappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease
View SamplesSnail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here that Snail1 plays also a key role in tumor associated fibroblasts since is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-b; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that tumor cells co-transplanted with Snail1 depleted fibroblasts show lower invasion than those xenografted with control fibroblasts. Finally Snail1 depletion in mice prevents the formation of breast tumors and decreased their invasion. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to its effect in EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial cells.
Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis.
Specimen part
View SamplesSerotonin in the mammary gland is known to regulate processes such as calcium homeostasis, tight junction permeability, and milk protein gene expression. The objective of this study was to discover novel genes, pathways and functions which serotonin modulates during lactation. The rate-limiting enzyme in the synthesis of non-neuronal serotonin is tryptophan-hydroxylase (TPH1). Therefore, we used TPH1 knock-out mice dams (serotonin deficient) and compared them to wild-type dams and also Tph1 deficient dams injected daily with 5-HTP. Mammary gland tissues were collected on day 10 of lactation and then analyzed by RNA sequencing. Overall design: Genome-wide gene expression profiles of 12 mouse mammary gland samples were evaluated using RNA sequencing; these 12 samples belong to wild-type dams (WT; n = 4), Tryptophan hydroxylase (Tph1) knock-out dams (KO; Tph1 deficient; n = 4), and Tph1 deficient dams injected daily with 5-HTP (RC; n = 4). Mammary tissues were collected on day 10 of lactation and then underwent RNA extraction, library generation, and subsequent sequencing.
Transcriptomic Analysis of the Mouse Mammary Gland Reveals New Insights for the Role of Serotonin in Lactation.
No sample metadata fields
View SamplesAIM: To detect differences in transcriptional profiles after knocking down Brca1, Bard1 or Wdr5, compared to a negative control in early reprogramming to pluripotency. DESCRIPTION: RNA-seq profiles of early reprogramming mouse embryonic fibroblasts (MEFs) transduced with lentivirus containing doxycycline-inducible OSKM factors to induce pluripotency . Before starting reprogramming, OSKM-MEFs were transfected with different siRNAs and then they were reprogrammed for 3 or 6 days. Overall design: The control sample consists of cells transfected with non-targeting siRNA. The other samples were transfected with either siBrca1, siWdr5 or siBard1. For every knockdown there is a biological replicate.
The corepressor NCOR1 and OCT4 facilitate early reprogramming by suppressing fibroblast gene expression.
Cell line, Subject
View SamplesAIM: To find molecular signatures associated to the siRNA-mediated knockdowns in order to be able to identify similarities among different knockdowns. DESCRIPTION: Each sample includes biological triplicates for 35 siRNA-mediated knockdowns targeting 30 chromatin-associated proteins during in early reprogramming to iPS at day 6. A daily timecourse from reprogramming cells, without treatment from MEFs until day 6 is also included in triplicate. Overall design: RNA was harvested for all samples in bulk and the CELSeq2 method was used to prepare the RNAseq libraries
The corepressor NCOR1 and OCT4 facilitate early reprogramming by suppressing fibroblast gene expression.
Cell line, Subject
View SamplesTo understand the fruit changes and mechanisms involved in the compatible grapevine-virus interaction, we analyzed the berry transcriptome in two stages of development (veraison and ripening) in the red wine cultivar Cabernet Sauvignon infected with Grapevine leaf-roll-associated virus-3 (GLRaV-3). Analysis of global gene expression patterns indicate incomplete berry maturation in infected berries as compared to uninfected fruit suggesting viral infection interrupts the normal berry maturation process.
Compatible GLRaV-3 viral infections affect berry ripening decreasing sugar accumulation and anthocyanin biosynthesis in Vitis vinifera.
Age, Specimen part
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