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GSE62107
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ligands activation of RXR modulate host antivarl response. We used microarray to determine if 9cRA could regulate the antiviral gene expression in LPS- and polyI:C triggered RAW264.7 cells.
Publication Title
Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The efficiency of central nervous system (CNS) remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study we show that expression of genes involved in the retinoid X receptor (RXR) pathway are decreased with aging in myelin-phagocytosing cells. Loss of RXR function in young macrophages mimics aging by delaying remyelination after experimentally-induced demyelination, while RXR agonists partially restore myelin debris phagocytosis in aged macrophages. The FDA-approved RXR agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in aging human monocytes to a more youthful profile. These results reveal the RXR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.
Publication Title
Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response. We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment. We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam celllike cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization. Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization.
Publication Title
Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
How neurons are wired to form precise circuits is crucial to understand the development of cortical functions. Glutamatergic pyramidal cell and GABAergic interneuron wire up the cortex through differentiated cellular events. However, little is known about the molecular mechanisms that underlie the unique features of interneuron wiring.
Publication Title
The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: A colorectal cancer classification system that associates cellular phenotype and responses to therapy. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response.
Publication Title
Colorectal cancer classification based on gene expression is not associated with FOLFIRI response.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Zinc finger nucleases (ZFN) are powerful tools for editing genes in cells. Here we use ZFNs to interrogate the biological function of human ADPGK, which encodes an ADP-dependent glucokinase (ADPGK), in tumour cell lines. The hypothesis tested is that ADPGK utilises ADP to phosphorylate glucose under conditions where ATP becomes limiting, such as hypoxia. We characterised two ZFN knockout clones in each of two tumour cell lines (H460 and HCT116). All four lines had frameshift mutations in all alleles at the target site in exon 1 of ADPGK, and were ADPGK-null by immunoblotting. ADPGK knockout had little or no effect on cell proliferation, but compromised the ability of H460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions, with clonogenic survival falling from 213% for the parental line to 6.40.8% (p=0.002) and 4.30.8% (p=0.001) for the two knockouts. A similar increased sensitivity to clonogenic cell killing was observed under anoxia. No such changes were found when ADPGK was knocked out in HCT116 cells, for which the parental line was less sensitive than H460 to anoxia and to hexokinase-2 silencing. While knockout of ADPGK in HCT116 cells caused few changes in global gene expression, knockout of ADPGK in H460 cells caused notable up-regulation of mRNAs encoding cell adhesion proteins. Surprisingly, we could discern no effect on glycolysis as measured by glucose consumption or lactate formation under oxic or anoxic conditions, or extracellular acidification rate (Seahorse XF analyser) under oxic conditions in a variety of media. However, oxygen consumption rates were generally lower in the ADPGK knockouts, in some cases markedly so. Collectively, the results demonstrate that ADPGK can contribute to tumour cell survival under conditions of high glycolytic dependence, but the phenotype resulting from knockout of ADPGK is cell line dependent and appears to be unrelated to priming of glycolysis.
Publication Title
Expression and role in glycolysis of human ADP-dependent glucokinase.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 75 Downloadable Samples
Illumina HiSeq 2500
Description
In the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of the aorta-gonad-mesonephros region from E9.5 embryos and E10.5 embryos sub-dissected into dorsal (AoD), ventral (AoV) and urogenital ridges (UGR) and pooled from between 15 and 34 embryos in three separate experiments.
Publication Title
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient derived xenograft (PDX) models is a promising platform to for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine environment on the gene expression of the engrafted human tumoral cells. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data from PDAC and hepatocellular carcinoma (HCC). Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable one from the other based in their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models are clearly different and more similar to their original tumor than to PDX models from the other tumor type. Interestingly, the main differences between pancreatic PDX models and human PDAC is the expression of genes involved in pathways related with extracellular matrix interactions and cell cycle regulation likely reflecting the adaptations of the tumors to the new environment. Furthermore, most of these differences are detected in the first passages after the tumor engraftment, indicating early phases of the adaptation process. In conclusion, different from conventional cancer cell lines, PDX models of PDAC retain similar gene expression profiles of PDAC. Expression changes are mainly related to genes involved in stromal pathways likely reflecting the adaptation to new environments. We also provide evidence of the stability of gene expression patterns over subsequent passages.
Publication Title
Transcriptional dissection of pancreatic tumors engrafted in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
In the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of OP9 cells grown in flat, submersed culture or reaggregate and cultured at the liquid-gas interface were compared.
Publication Title
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.
Publication Title
Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids.
Sample Metadata Fields
Specimen part
View Samples