Microarray analysis was performed to determine the transcriptional profiles of NKT, CD1d-aGC+ Va24-, and CD4 T cells.
A naive-like population of human CD1d-restricted T cells expressing intermediate levels of promyelocytic leukemia zinc finger.
Specimen part
View SamplesTumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice there is an influx of tumor macrophages that polarize towards wound repair and immune suppression.
Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
Specimen part, Treatment, Time
View SamplesWe conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy as well as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring.
Effects of moderate drinking during pregnancy on placental gene expression.
Specimen part
View SamplesA QTL intercross was performed bewteen C57BL/6J and KK/HIL for albuminurea, asthma and cardiovascular related phenotypes. Several QTL were identified for most phenotypes. We performed microarray analysis from liver samples to identify genes differentially expressed between the parental strains. The results helped us narrow down the QTL and identify the candidate genes based on differential expression between the parental strains.
A major X-linked locus affects kidney function in mice.
Sex, Specimen part
View SamplesRetinopathy of prematurity (ROP) is the most common cause of childhood blindness worldwide and is caused by oxygen therapy necessary to prevent mortality after premature birth. We have previously demonstrated the efficacy of systemic hypoxia inducible factor (HIF) stabilization through HIF prolyl hydroxylase inhibition (HIF PHi) in protecting retinal vasculature from oxygen toxicity in a mouse model of ROP or oxygen induced retinopathy (OIR). We definitively demonstrated that hepatic HIF-1 can be activated to confer this protection using systemic dimethyloxalylglycine (DMOG) to prevent HIF-1a degradation. In this study we compare Roxadustat, a small molecule stabilizer of HIF-1 currently in phase 3 clinical trials for increasing erythropoiesis in adult patients with chronic kidney disease, to DMOG. We demonstrate that Roxadustat induces vascular protection during hyperoxia to induce the coordinated sequential growth of retinal vasculature with a 3-fold reduction in oxygen induced capillary loss (p-=0.001). In order to define the molecular mechanism of protection, we further compared the transcriptome of both liver and retina after systemic treatment with Roxadustat or DMOG. Similar gene expression profiles were identified in liver but very different effects on transcription were found in retinal tissues because Roxadustat, in contrast to DMOG, directly targets retina, confirmed by western blot and by rescue of the hepatic HIF-1 KO, two criteria that DMOG treatment is unable to fulfill. Systems pharmacologic analysis demonstrates that Roxadustat induces typical HIF regulated genes critical to aerobic glycolysis in liver and retinal tissues whereas DMOG, acting through either secreted hepatokines or by influence of systemic DMOG, downregulates cell adhesion/extracellular matrix interaction pathways while increasing expression of histone cluster genes. Stratification of liver transcriptomes to secreted gene products again shows close consensus of hepatic genes induced by both small molecules, and includes upregulation of a plethora of angiogenic proteins such as plasminogen activator inhibitor (PAI-1), erythropoietin (EPO), and orosomucosoid 2 (ORM2). Secondary validation of these transcripts by serum ELISA confirms secretion of EPO and PAI-1 into blood from liver. These findings definitively demonstrate that HIF stabilization can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect, hepatic HIF-1 stabilization and increased serum angiokines. Systems pharmacology analysis therefore explains why intermittent, low dosage of small molecule HIF stabilizers creates a profound protective phenotype, because both pathways can take advantage of cytoprotection induced by the liver and by retina synergistically. These data provide a rationale for considering low dose, intermittent systemic administration of Roxadustat, currently in phase 3 trials in adults with chronic kidney disease, to eradicate ROP in children. Overall design: RNA-Seq of mice treated with PBS (control), DMOG, or Roxadustat from liver or retina.
Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesRecent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesRecent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesWe sought to determine genes whose expression changed upon treatment with a selective inhibitor of class I PI3 kinase.
Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models.
Cell line
View SamplesGWAT store most of the TAG in mice, ob/ob mice is an obese mice. Ob/ob/Fsp27-/- mice are lean when compared with ob/ob mice. The GWAT weight was dramatically reduced in ob/ob/Fsp27-/- mice.
Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice.
Sex, Age, Specimen part
View Samples