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Homo sapiens
43 Downloadable Samples
NextSeq 500
Description
Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-alpha (-58%), IFN-gamma (-47%) and IL-beta (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Peripheral Mononuclear Cells taken from 11 healthy donors, prior to administration of metformin and after 5 days of metformin. Samples were stimulated with Mycobacterium tuberculosis lysate or cultured unstimulated for 4 hours. Total 88 samples, with 11 clinical replicates.
Publication Title
Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- NextSeq 500
Description
Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-a (-58%), IFN-gamma (-47%) and IL-1ß (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Ex vivo blood RNA samples analyzed from 11 healthy donors, prior to administration of metformin (control) and after 5 days of metformin (test). Total 22 samples, with 11 clinical replicates.
Publication Title
Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Recent studies have demonstrated that upon encountering a pathogenic stimulus, robust metabolic rewiring of immune cells occurs. A switch away from oxidative phosphorylation to glycolysis, even in the presence of sufficient amounts of oxygen (akin the Warburg effect), is typically observed in activated innate and adaptive immune cells and is thought to accommodate adequate inflammatory responses. However, whether the Warburg effect is a general phenomenon applicable in human monocytes exposed to different pathogenic stimuli is unknown. Our results using human monocytes from healthy donors demonstrate that the Warburg effect only holds true for TLR4 activated cells. Although activation of other TLRs leads to an increase in glycolysis, no reduction or even an enhancement in oxidative phosphorylation is observed. Moreover, specific metabolic rewiring occurs in TLR4 vs. TLR2 stimulated cells characterized by altered gene expression profiles of pathways related to metabolism, changes in spare respiratory capacity of the cells and differential regulation of mitochondrial enzyme activity. Similarly, results from ex vivo and in vivo studies demonstrate metabolic rewiring of immune cells that is highly dependent on the type of pathogenic stimulus. Although the Warburg effect is observed in human monocytes after TLR4 activation, we propose that this typical metabolic response is not applicable to other inflammatory signalling routes including TLR2 in human monocytes. Instead, each pathogenic stimulus and subsequently activated inflammatory signalling cascade induces specific metabolic rewiring of the immune cell to accommodate an appropriate response.
Publication Title
Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- NextSeq 500
Description
Cell-autonomous circadian oscillations strongly influence tissue physiology and pathophysiology of peripheral organs. Recent in vivo findings in the heart demonstrate that the circadian clock controls oscillatory gene expression programs in the adult myocardium. However, whether in vitro human embryonic stem (ES) cell-derived cardiomyocytes can establish circadian rhythmicity is unknown. Here we report that while undifferentiated human ES cells do not possess a functional clock, oscillatory expression of known core clock genes emerges during directed cardiac differentiation, with robust rhythms in day 30 cardiomyocytes. Our data reveal a stress related oscillatory network of genes that underlies a time-dependent response to doxorubicin, a frequently used anti-cancer drug with cardiotoxic side effects. These results provide a set of oscillatory genes that is relevant to functional cardiac studies and that can be deployed to uncover the potential contribution of the clock to other processes such as cardiac regeneration. Overall design: Human embryonic stem cells (ES cells) were differentiated via a directed differentiation protocol in vitro towards cardiomyocytes for a period of 30 days. Cardiomyocytes were synchronized with dexamethasone and triplicate samples for RNA extraction and sequencing were taken every 4 hours for 48 hours in total. RNA was then extracted using TRIzol, barcoded and amplified following the CEL-Seq protocol.
Publication Title
Circadian networks in human embryonic stem cell-derived cardiomyocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 1 Downloadable Sample
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 1 Downloadable Sample
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Utilizing Affymetrix ATH1 microarrays to analyze transposon expression in DNA methylation mutants, and RNAi mutants, compared to wildtype.
Publication Title
miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The lack of suitable animal models reflecting chronically relapsing inflammation and tissue remodeling have hindered fibrosis research in inflammatory bowel diseases (IBD). This study investigated changes in connective tissue in a chronic murine model using different cycles of dextran sodium sulphate (DSS) to mimic the relapsing nature of the disease.
Publication Title
Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
SRP059989- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
By means of 3' end sequencing we provide a genome-wide, high-resolution polyadenylation map of the human heart. By sequencing 5 control en 5 dilated cardiomyopathy (DCM) myocardial specimens we investigate the difference in alternative polyadenylation (APA) in healthy and diseased hearts.
Publication Title
Genome-Wide Polyadenylation Maps Reveal Dynamic mRNA 3'-End Formation in the Failing Human Heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Increased levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) have been detected in fibrotic strictures in Crohns disease. In a murine model of chronic inflammation, fibrosis was associated with an increase in TIMP-1 and inhibition of matrix metalloproteinase (MMP)-mediated degradation. We investigated the effect of TIMP-1 deficiency on the colonic gene expression in acute and chronic murine models of colitis, using whole genome gene expression arrays.
Publication Title
Genetic Deletion of Tissue Inhibitor of Metalloproteinase-1/TIMP-1 Alters Inflammation and Attenuates Fibrosis in Dextran Sodium Sulphate-induced Murine Models of Colitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
The similarity in gene-expression profiles suggest that PGL2, like SDHD, is involved in the functionality of the SDH complex, and that tumor formation in these three subgroups involves the same pathways as in SDH linked paragangliomas. We were not able to clarify the identity of PGL2 on 11q13. The lack of differential gene-expression of chromosome 11 genes might indicate that chromosome 11 loss, as demonstrated in SDHD-linked paragangliomas, is an important feature in the formation of a paraganglioma regardless of the genetic background.
Publication Title
Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas suggest a common pathway to tumorigenesis.
Sample Metadata Fields
No sample metadata fields
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