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SRP115480
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
- 8 Downloadable Samples
- Illumina HiSeq 4000
Description
Human tumors are infiltrated by various immune cells, including CD8 T cells. CD8 T cells express unique receptors that can recognize peptides at the host's cells, including tumor cells. After probing the antigen specificity of ex-vivo tumor-infiltrating CD8 T cells from human tumors, we hypothesized that expression of CD39 was correlated with tumor-specificity. The present experiment aims at better characterizing ex-vivo CD39+ vs CD39- CD8 T cells. Overall design: CD39- and CD39+ CD8 T cells were FACS sorted from 8 fresh tumor samples and their RNA extracted for transcriptomic profiling.
Publication Title
Bystander CD8<sup>+</sup> T cells are abundant and phenotypically distinct in human tumour infiltrates.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- NextSeq 500
Description
The goal of this study was to determine how decreased mitochondrial citrate export influences gene expression in Drosophila larvae. RNA was isolated from Drosopohila sea mutants, which exhibiti decreased mitochondrial citrate transport activity, and a genetically-matched control strain during mid-L3 development. Overall design: Larvae were collected as described in Li, H., Tennessen, J. M. Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry (GC-MS)-based Metabolomics. J. Vis. Exp. (136), e57847, doi:10.3791/57847 (2018). RNA was purified from staged mid-L3 larvae using a RNeasy Mini Kit (Qiagen). Sequencing was performed using an Illumina NextSeq500 platform with 75 bp sequencing module generating 41 bp paired-end reads. After the sequencing run, demultiplexing was performed with bcl2fastq v2.20.0.422.
Publication Title
A <i>Drosophila</i> model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
In the current study, we performed transcriptome profiling of the mouse PFC to determine the dynamic changes in the Prefrontal cortex (PFC)after repeated cocaine treatment. In the current study, we observed dynamic changes in the transcriptome profiling of the PFC of repeated-cocaine treated mice, and found that distinct pathways were involved in the acute, sub-acute, and chronic stages of cocaine withdrawal. The main findings of our results include: 1) energy metabolism and protein metabolism pathways showed gradual or fluctuant decrease after cocaine withdrawal; 2) ERK pathway showed persistent changes after cocaine withdrawal; 3) plasticity related pathways, such as long-term potentiation, the regulation of the actin cytoskeleton, and the axon guidance pathway, showed a fluctuant increase after cocaine withdrawal. Our results suggest that maladaptive neural plasticity associated with psychostimulant dependence may be an ongoing degenerative process with dynamic changes in the gene network at different stages of withdrawal. Overall design: The bilateral PFC was excised from each animal at either 2 h, 24 h, or 7 days after the final injection of cocaine. To account for inter-animal variations, we obtained 2 biological replicates for each treatment group, with each replicate representing the PFCs pooled from 5 animals. Pair-end 75-nt sequencing was performed using the Illumina HiSeq2000.
Publication Title
Dynamic Expression Changes in the Transcriptome of the Prefrontal Cortex after Repeated Exposure to Cocaine in Mice.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Subject
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
How animals coordinate gene expression in response to starvation is an outstanding problem closely linked to aging, obesity, and cancer. Newly hatched Caenorhabditis elegans respond to food deprivation by halting development and promoting long-term survival (L1 diapause), thereby providing an excellent model to study starvation response. Through a genetic search, we have discovered that the tumor suppressor Rb critically promotes survival during L1 diapause and likely does so by regulating the expression of genes in both insulin-IGF-1 signaling (IIS)-dependent and -independent pathways mainly in neurons and the intestine. Global gene expression analyses suggested that Rb maintains the starvation-induced transcriptome and represses the re-feeding induced transcriptome, including the repression of many pathogen/toxin/oxidative stress-inducible and metabolic genes, as well as the activation of many other stress-resistant genes, mitochondrial respiratory chain genes, and potential IIS receptor antagonists. Notably, the majority of genes dysregulated in starved L1 Rb(-) animals were not found to be dysregulated in fed conditions. Together, these findings identify Rb as a critical regulator of the starvation response and suggest a link between functions of tumor suppressors and starvation survival. These results may provide mechanistic insights into why cancer cells are often hypersensitive to starvation treatment.
Publication Title
The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This study aimed to identify differential expressed genes before and after treatment with the compound sulforaphene, using the MDA-MB-453 breast cancer cell line as a model.
Publication Title
Sulforaphene inhibits triple negative breast cancer through activating tumor suppressor Egr1.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Race
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
From our previous data, we found that loss of ATAD3A gene expression in breast cancer cells results in loss of cell motility in vitro and metastasis in vivo. To obtain a better understanding of oncogenic pathway of ATAD3A, we have established the stable ATAD3A knockdown MDA-MB-231 cells using lentiviral strategy.
Publication Title
Mitochondrial ATAD3A combines with GRP78 to regulate the WASF3 metastasis-promoting protein.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Cancer cells utilize a unique form of aerobic glycolysis, called the Warburg effect, to efficiently produce the macromolecules required for proliferation. Here we show that a metabolic program related to the Warburg effect is used during normal Drosophila development and regulated by the fly ortholog of the Estrogen-Related Receptor (ERR) family of nuclear receptors. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triacylglyceride stores, and elevated levels of circulating sugars. Metabolomic profiling revealed that the pathways affected in these mutants correspond to those used in the Warburg effect. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program supporting the dramatic growth that occurs during larval development. This study suggests that mammalian ERR family members may promote cancer by directing a metabolic state that supports proliferation.
Publication Title
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- NextSeq 500
Description
Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/b-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development. Overall design: RNA-sequencing of peripheral blooof 10 LM patients and 9 control subjects
Publication Title
Alterations of the MEK/ERK, BMP, and Wnt/β-catenin pathways detected in the blood of individuals with lymphatic malformations.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples