Filters
Technology
Platform
GSE137985
Mus musculus
50 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Background: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease, so that effective therapies can be developed. Almost all pre-clinical studies evaluating skeletal muscle’s response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. Methods: To create the four cohorts of PDX mice evaluated in this study, tumors resected from four pancreatic ductal adenocarcinoma (PDAC) patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumor-burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA revealed key differences between their transcriptomes in response to cancer as well. Indeed, upregulated genes in the diaphragm were enriched for extracellular matrix (ECM) protein-encoding genes and genes related to the inflammatory response, and downregulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed upregulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis and enrichment of downregulated genes encoding ECM proteins. Conclusions: These data suggest that distinct biological processes account for wasting in different skeletal muscles in response to the same tumor burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Serum levels of interleukin-8 (IL-8) are increased in the serum of people with pancreatic cancer and associated with the loss of body weight and low muscle mass. We have identified that systemic (intraperitoneal) injection of IL-8 into mice induces significant skeletal muscle atrophy. Transcriptional profiling of muscle harvested from these same mice identified the genes and biological processes associated with this IL-8 induced atrophy including gene clusters related to chromatin modification, muscle cell differentiation, and ubiquitin ligase complex.
Publication Title
IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The Akita mutation (C96Y) in the insulin gene results in early onset diabetes in both humans and mice. Expression of the mutant proinsulin (C96Y) causes endoplasmic reticulum (ER) stress in pancreatic -cells and consequently the cell activates the unfolded protein response (UPR). Since the proinsulin is terminally misfolded however, the ER stress is irremediable and chronic activation of the UPR eventually activates apoptosis in the cell population.
Publication Title
IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Arabidopsis thaliana
- 2 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The transcript levels of 560 genes were decreased (less than two-fold), while those of 312 genes were increased (more than two-fold) in the KO-HsfA1d/A1e plants compared with the wild-type plants. The transcript levels of HsfA2, HsfA7a, HsfA7b, HsfB1, and HsfB2a were down-regulated in the KO-HsfA1d/A1e
Publication Title
HsfA1d and HsfA1e involved in the transcriptional regulation of HsfA2 function as key regulators for the Hsf signaling network in response to environmental stress.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have developed a new conditional transgenic mouse showing that MLL-ENL, at an endogenous-like expression level, induces leukemic transformation selectively in LT-HSCs. To investigate the molecular mechanism of leukemic transformation in LT-HSCs conditionally expressing MLL-ENL, we preliminarily performed comprehensive gene expression profiling of CreER-transduced LT-HSCs and ST-HSCs using cDNA microarray analysis.
Publication Title
Plzf drives MLL-fusion-mediated leukemogenesis specifically in long-term hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The role of microRNAs (miRNA) in first cell fate choice of the preimplantation mouse embryo remains unresolved, as gene expression and knockout data are conflicting. This cell fate choice generates the extraembryonic lineage of the trophoblast and the embryonic lineage of the epiblast (inner cell mass). The trophoblast differentiates into polar and mural cells, where polar cells contribute to placental development and mural cells to the implantation process and Reicherts membrane. The inner cell mass further differentiates into the epiblast and primitive endoderm. We used stem cell lines that can be derived from the trophoblast and epiblast lineages to address the role of miRNAs in early lineage cell fate specification and determination. Using embryonic stem cells (ESC) and trophoblast stem cells (TSC) as starting and ending states of cell development we identified a network of TSC expressed miRNAs that are enriched in ESC targets mRNA. We used constitutive and inducible expression of TSC enriched miRNAs in ESC and show that they can drive cell morphology and gene expression profiles similar to trophoblast. Additionally we show that this process required HDAC2 inhibition and is miRNA specific, as cardiac specific miR-1 could not induce trophoblast under these conditions. In contrast to embryo derived and Cdx2 induced trophoblast cells, miRNAs promote a mural TE like cell phenotype. Transplantation into preimplantation mouse embryos showed that miRNA-induced trophoblast preferentially contributes to the mural trophoblast in both the blastocyst and the Reicherts membrane. Our data support a role for miRNAs and HDACs in the specification of the trophoblast and potentially the polar and mural cell types.
Publication Title
Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
We performed RNA-seq to quantify gene expression changes in adult worms upon knockdown of transcription factor unc-62/Homothorax. unc-62 is a developmental regulator that binds proximal to age-regulated transcripts and modulates lifespan. In the intestine (in which tissue-specific unc-62 knockdown increases lifespan), we identify multiple effects of unc-62 knockdown linked to extension of longevity. First, unc-62 RNAi decreases the expression of yolk proteins (vitellogenins) that aggregate in the body cavity and become toxic in old age. Second, unc-62 RNAi results in a broad increase in expression of intestinal genes that typically decrease expression with age, suggesting that unc-62 activity balances intestinal resource allocation between yolk protein expression and fertility on the one hand and somatic functions on the other. Overall design: mRNA profiling by Illumina HiSeq of 3 biological replicates of day 4 adult Caenorhabditis elegans that were fed either control or unc-62 RNAi beginning at day 1 of adulthood.
Publication Title
Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
We used RNA-seq to discover that gene expression changes during aging are attenuated in elt-2 overexpressors relative to controls Overall design: Whole-worm mRNA was sequenced from worms over-expressing elt-2 and control worms. Five biological replicates were collected for each condition.
Publication Title
Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGF/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we used microarrays to identify genes whose expression is regulated by the JNK pathway during dorsal closure of the Drosophila embryo.
Publication Title
The Drosophila serine protease homologue Scarface regulates JNK signalling in a negative-feedback loop during epithelial morphogenesis.
Sample Metadata Fields
Specimen part
View Samples