This SuperSeries is composed of the SubSeries listed below.
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Specimen part
View SamplesProtein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a bottom-up approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Specimen part
View SamplesProtein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a bottom-up approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Specimen part
View SamplesImmortalized kidney tubular cells were obtained from immortomice. The gene Glis2 was knocked down by adenoviral-mediated infectipon of specific shRNAs
No associated publication
Specimen part
View SamplesWe extracted nascent plasma cell tumor (PCT) cells from within inflammatory granulomas (OG) isolated from intraperitoneal pristane-injected BALB/c.iMyc E mice at five different time points during tumor progression. We used laser capture micro-dissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice
Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia.
Specimen part
View SamplesOur goal was to identify gene expression patterns that correlated with prevention of autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part, Treatment
View SamplesThe objective of the overall study was to determine the effects of oral vitamin D supplementation on alveolar macrophages from human subjects. In this substudy, subjects treated with vitamin D (intervention group) in paired analysis had small, but significant effects on immune-related differential gene expression pre versus post supplementation.
Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial.
Specimen part, Treatment, Subject
View SamplesThere is a critical need in cancer therapeutics to identify targeted therapies that will improve outcomes and decrease toxicities compared to conventional, cytotoxic chemotherapy. Ewing sarcoma is a highly aggressive bone and soft tissue cancer that is caused by the EWS-FLI1 fusion protein. Although EWS-FLI1 is specific for cancer cells, and required for tumorigenesis, directly targeting this transcription factor has proven challenging. Consequently, targeting unique dependencies or key downstream mediators of EWS-FLI1 represent important alternative strategies. We used gene expression data derived from a genetically defined model of Ewing sarcoma to interrogate the Connectivity Map and identify a class of drugs, iron chelators, that downregulate a significant number of EWS-FLI1 target genes. We then identified ribonucleotide reductase M2 (RRM2), the iron-dependent subunit of ribonucleotide reductase (RNR), as one mediator of iron chelator toxicity in Ewing sarcoma cells. Inhibition of RNR in Ewing sarcoma cells led to apoptosis and cell death in vitro and attenuated tumor growth in vivo in a xenograft model. Additionally, we discovered that the sensitivity of Ewing sarcoma cells to inhibition or suppression of RNR is mediated, in part, by high levels of SLFN11, a protein that sensitizes cells to DNA damage. This work demonstrates a unique dependency of Ewing sarcoma cells on RNR and supports further exploration of clinically used inhibitors of RNR as a therapeutic approach in treating this cancer.
Gene expression signature based screening identifies ribonucleotide reductase as a candidate therapeutic target in Ewing sarcoma.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View SamplesOur goal was to identify gene expression patterns that correlated with treatment of established autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part, Treatment
View Samples