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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Analysis of glioblastoma tumor cell-specific gene expression profiles of distinct histological phenotypes

ABSTRACT: Here, we analyzed patient-derived glioblastoma xenografts generated in the mouse brain that give rise to three different histological phenotypes: (i) a highly invasive phenotype (ii) a highly angiogenic phenotype and (iii) an intermediate phenotype. Cell type-specific transcriptomic profiles of tumor and stromal endothelial cells were analyzed to reveal phenotype-specific gene expression patterns and the reciprocal crosstalk between tumor and stromal endothelial cells. This part of the study contains the analysis of the patient-derived tumor cells. The analysis of the stromal endothelial cells of the host mice is found under E-MTAB-3949.

ORGANISM(S): Homo sapiens

SUBMITTER: Tony KAOMA

PROVIDER: E-MTAB-3948 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Analysis of glioblastoma tumor cell-specific gene expression profiles of distinct histological phenotypes

Project description:Here, we analyzed patient-derived glioblastoma xenografts generated in the mouse brain that give rise to three different histological phenotypes: (i) a highly invasive phenotype (ii) a highly angiogenic phenotype and (iii) an intermediate phenotype. Cell type-specific transcriptomic profiles of tumor and stromal endothelial cells were analyzed to reveal phenotype-specific gene expression patterns and the reciprocal crosstalk between tumor and stromal endothelial cells. This part of the study contains the analysis of the stromal endothelial cells of the host mice. The analysis of the patient-derived tumor cells is found under E-MTAB-3948.

2016-06-30 | E-MTAB-3949 | biostudies-arrayexpress

Microarray of young adults of endu-2(tm4977) loss of function mutant and endu-2(tm4977);Ex[endu-2::EGFP] rescue strain grown up at 25°C

Project description:The poly-U specific endoribonuclease ENDU-2 plays an important role in maintaining germline immortality in C. elegans. The endu-2 loss-of function mutants display a mortal germline phenotype at 20°C but not at 15°C. At 25°C, the mortal germline phenotype is enhanced. In addition, an extrachromosomal endu-2::EGFP transgene rescues the mutant phenotype. In order to investigate the role of ENDU-2 on mRNA abundancy, a microarray analysis was performed via comparing young adults of endu-2(tm4977) loss of function mutant and endu-2(tm4977);Ex[endu-2::EGFP] rescue strain grown up at 25°C. As ENDU-2 affects maternal inheritance, grouped animals for comparison were derived from one grandmother (endu-2(tm4977);Ex[endu-2::EGFP]) to ensure the same maternal inheritance at the parental generation.

2020-10-31 | E-MTAB-7993 | biostudies-arrayexpress

Expression data from cultured primary mouse dermal fibroblasts

Project description:In previous investigations, we detected that growth of melanoma cells in mice depleted for adam9 is enhanced. This resulted from molecular alterations in stromal cells cross-communicating to tumor cells and from constitutively altered expression of some molecules, e.g., TIMP1 in stromal fibroblasts lacking adam9. We used microarray analysis to identify the gene expression alterations occurring in stromal cells upon adam9 deletion which lead to the molecular alterations observed and contribute to the tumor phenotype. Primary fibroblasts from adam9 KO and WT mice were cultured in standard conditions to address constitutive gene alterations.

2014-03-28 | E-GEOD-56304 | biostudies-arrayexpress

An IL-1β driven neutrophil-stromal cell axis fosters a BAFF-rich microenvironment in multiple myeloma

Project description:Neutrophils are the most abundant nucleated cell type in the bone marrow. A pro-tumor bias in this cell type may have implications for bone-marrow residing malignancies, such as multiple myeloma. Here, we generated single cell transcriptomic overviews of the entire myeloid compartment, including the entire neutrophilic lineage, of the bone marrow of 6 newly diagnosed myeloma patients, 5 treated myeloma patients and 4 non-cancer controls. We find dat mature neutrophils in myeloma patients, both newly diagnosed and treated, have an activated and pro-inflammatory phenotype, accompanied by increased transcription of pro-inflammatory cytokines, such as IL-1β, and myeloma cell survival factors, such as BCMA-ligand BAFF/TNFSF13B. Moreover, inflammatory stromal cells can activate naive neutrophils to acquire an inflammatory phenotype as is seen in patients. Previously, we have shown that inflammatory stromal cells characterized the bone marrow of newly diagnosed myeloma patients. Here, we generate single cell RNA sequencing dataset of non-hematopoietic bone marrow cells of patients after induction treatment, high-dose melphalan, stem cell transplantation and consolidation treatment. We show that this intensive treatment reduced, but did not normalize, stromal inflammation.

2023-03-31 | E-MTAB-12760 | biostudies-arrayexpress

Endothelin2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis

Project description:Endothelin signaling is required for neural crest migration and homeostatic regulation of blood pressure. Here we report that constitutive over-expression of Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by inhibiting endothelial cell (EC) migration across the retinal surface and subsequent EC invasion into the retina. Developing endothelial cells exist in one of two states: tip cells at the growing front, and stalk cells in the vascular plexus behind the front. This division of endothelial cell states is one of the central organizing principle of angiogenesis. In the developing retina, Edn2 over-expression leads to over-production of endothelial tip cells by both morphologic and molecular criteria. Spatially localized over-expression of Edn2 produces a correspondingly localized endothelial response. Edn2 over-expression in the early embryo inhibits vascular development at mid-gestation, but Edn2 over-expression in developing skin and brain has no discernable effect on vascular structure. Inhibition of retinal angiogenesis by Edn2 requires expression of Endothelin receptor A (Ednra) but not Ednrb in the neural retina. Taken together, these observations imply that the neural retina responds to Edn2 by synthesizing one or more factors that promote the endothelial tip cell state and inhibit angiogenesis. The response to Edn2 is sufficiently potent that it over-rides the activities of other homeostatic regulators of angiogenesis, such as vascular endothelial growth factor. Z/Edn2 females were crossed to Six3-Cre; Six3-Cre males. Postnatal P8 pups were genotyped for the Z/Edn2 allele by detection of Laz-Z activity in tail clips. Retinas from 2 - 3 pups were pooled for each data point.

2014-01-01 | E-GEOD-50059 | biostudies-arrayexpress

Bulk RNA sequencing of endothelial-derived and non-endothelial-derived BMSCs and OLCs of VE-Cadherin-Cre;LoxP-tdTomato mice

Project description:We performed lineage tracing experiments using VE-Cadherin-Cre;LoxP-tdTomato mice. In these mice, endothelial cells (ECs) and their progeny are permanently marked by tdTomato fluorescence. We found that a substantial subset of stromal cells is derived from ECs, as indicated by their tdTomato expression. These findings support the notion that endothelial to mesenchymal transition (EndoMT) contributes to hematopoietic bone marrow niche formation in mice. Here we sought to determine the transcriptomic differences between endothelial-derived (tdTomato-positive) and non-endothelial-derived (tdTomato-negative) bone marrow stromal cells (BMSCs) and osteo/chondrolineage progenitor cells (OLCs). Murine niche populations were obtained from collagenased bone fraction of VE-Cadherin-Cre;LoxP-tdTomato mice at 3 weeks (n=2) or 11 weeks (n=2) of age. BMSCs (CD45-TER119-CD31-CD144-SCA-1+ CD51+ cells) and OLCs (CD45-TER119-CD31-CD144-Sca1-CD51+ cells) were FACS-purified and sequenced.

2021-01-25 | E-MTAB-10020 | biostudies-arrayexpress

Apoptosis regulation by Kaposi’s sarcoma microRNAs

Project description:Herpesviruses are known to encode micro (mi)RNAs and to use them to regulate the expression of both viral and cellular genes. The genome of Kaposi’s sarcoma herpesvirus (KSHV) encodes a cluster of twelve miRNAs, which are abundantly expressed during both latency and lytic infection. Relatively few cellular targets of KSHV miRNAs are known. Here, we used a microarray expression profiling approach to analyze the transcriptome of both B lymphocytes and endothelial cells stably expressing KSHV miRNAs and monitor the changes induced by the presence of these miRNAs. We generated a list of potential cellular targets by looking for miRNA seed-match-containing transcripts that were significantly down regulated upon KSHV miRNAs expression. Interestingly, the overlap of putative targets identified in B lymphocytes and endothelial cells was minimal, suggesting a tissue-specific target-regulation by viral miRNAs. Among the putative targets, we identified caspase 3, a critical factor for the control of apoptosis, which we validated using luciferase reporter assays and western blotting. In functional assays we obtained further evidence that KSHV miRNAs indeed protect cells from apoptosis. Single-channel hybridization to Affymetrix oligonucleotides microarrays. DG75 and EA.hy926 cells were transducted in triplicates with the K10/12 and K12/12 lentiviral constructs expressing the KSHV miRNAs, or with a GFP-expressing construct as control. The K10/12 construct expressed only the ten intronic miRNAs miR-K12-1 to 9 and miR-K12-11 while the K12/12 construct also expressed miR-K12-10 and miR-K12-12 in addition.

2011-10-27 | E-GEOD-18946 | biostudies-arrayexpress

The human placental sexome differs between trophoblast epithelium and villous vessel endothelium

Project description:As susceptibility to many adult disorders originates in utero, we here hypothesized that fetal sex influences gene expression in placental cells and produces functional differences in human placentas. We found that fetal sex differentially affects gene expression in a cell-phenotype dependent manner among all four placental cell-phenotypes studied: cytotrophoblasts, syncytiotrophoblasts, arterial endothelial cells and venous endothelial cells. The markedly enriched pathways in males were identified to be signaling pathways for graft-versus-host disease as well as the immune and inflammatory systems, both supporting the hypothesis that there is reduced maternal-fetal compatibility for male fetuses. Our study is the first microarray study investigating sexual dimorphism in purified and characterized somatic cells from a single human tissue, the placenta, that underlines the importance of considering fetal sex as an independent variable in any work using human placenta. Arterial and venous endothelial cells were isolated from eight different placentas, four of each sex. A total of ten placentas were used for isolation of cytotrophoblasts and six for syncytiotrophoblasts, with equal numbers from each sex.

2013-10-01 | E-GEOD-44368 | biostudies-arrayexpress

Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function (part 1: Proteins transferred from cancer-associated fibroblasts to endothelial cells : trans-SILAC)

Project description:Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we unveil a mechanism of cell-cell communication between CAFs with a myofibroblast phenotype and endothelial cells (ECs) based on intercellular protein transfer through extracellular vesicles (EVs). CAFs transfer proteins to ECs, including plasma membrane receptors, which we have identified by using mass spectrometry-based proteomics. Using THY1 as an example of transferred plasma membrane-bound protein, we show that CAF-derived proteins can influence how ECs interact with other cell types. Here, we show that CAFs produce high amounts of matrix-bound EVs that have a key role in protein transfer. Hence, our work paves the way for further studies to understand how CAF-derived matrix-bound EVs influence tumor pathology by regulating functions of neighboring cancer, stromal and immune cells.

2024-02-16 | PXD034450 | Pride

Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function (part 4: Proteomic analysis of pCAFs expressing high and low α-SMA protein levels)

2024-02-16 | PXD034519 | Pride

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