This SuperSeries is composed of the SubSeries listed below.
Brain transcriptional and epigenetic associations with autism.
Age, Specimen part, Disease, Disease stage, Subject
View SamplesTranscriptome analysis was used to identify gene expression changes during development of sunitinib resistance in a renal cell carcinoma patient-derived xenograft (PDX) model. During the response phase, tumors exhibited a 91% reduction in volume, characterized by induction of TNFRSF1A, TNFAIP3, NFKB2, CCL2, CCL20, BIRC3, and MOAP1. Ingenuity Pathway Analysis indicated decreased expression of cell survival genes during tumor response to sunitinib. In this model, after 4 weeks of treatment, tumors developed resistance despite continued administration of the tyrosine kinase inhibitor (TKI) sunitinib (40 mg/kg/d p.o.). Resistance was associated with increased expression of VEGFA, EPO, IL-8, ANGPT2, TNFRSF12, MAPK3/7, MAPKBP1, and increased cell survival genes, suggesting activation of angiogenesis and MAPK/ERK pathways. Tumor lysate mRNA evaluated for murine gene expression to examine the contribution of host effects, indicated that tumor response was associated with downregulation of immune cell trafficking, cellular movement, and inflammatory response genes. During tumor escape, genes associated with cellular movement, inflammatory response, and immune cell trafficking were strongly induced, along with intratumoral accumulation of myeloid derived suppressor cells (MDSC), indicating a role for host factors during emergence of sunitinib resistance. The same PDX model was used to assess anti-tumor efficacy of sunitinib combined with MEK inhibitor (MEKi) PD-0325901 (4 mg/kg/d p.o.) using different schedules. The most effective treatment regimen was either continuous treatment with both drugs or switching from sunitinib to PD-0325901 monotherapy at d30, which reduced tumor volume by 78.6% (p=0.0241) and 88.5% (p=0.0068), respectively. The combination of MEKi with TKI (sunitinib, axitinib, or pazopanib) suppressed levels of phospho-MEK1/2 and phospho-ERK1/2, and decreased intratumoral MDSC. Thus, continuous treatment with sunitinib alone did not maintain tumor response, and addition of a MEKi abrogated resistance leading to prolonged survival.
No associated publication
Specimen part
View SamplesAutism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.
Brain transcriptional and epigenetic associations with autism.
Age
View SamplesWe used an Illumina Gene Expression Array to understand in more detail how T387 phosphorylation affects ISG induction. mRNA preparations from U6A cells expressing wild-type or T387A STAT2, treated with IFN- for 0, 4, 8, or 24 h, were analyzed.
Negative regulation of type I IFN signaling by phosphorylation of STAT2 on T387.
Specimen part, Cell line
View SamplesHCMV latnecy within hematopoetic precursor cells was evaluated by infecting cells and establishing latency using a recombinant virus that allows for labeing of RNA species only in the context of a viral infection thereby allowing purification of these transcripts from mock infected cells.
No associated publication
Cell line, Treatment
View SamplesTo study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. These mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength
No associated publication
Age, Specimen part
View SamplesBone marrow macrophages were cultured from 16 week old apoE-deficient F2 mice from an AKRxDBA/2 intercross
Sex specific gene regulation and expression QTLs in mouse macrophages from a strain intercross.
No sample metadata fields
View SamplesNote: non-normalized values and associated raw data cannot be located by the submitter
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesThe aim of this study is to characterize transcriptional changes induced by maternal diet in several adult tissues and to test whether differences in DNA methylation or microRNA expression could explain these changes.
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesThe aim of this study is to characterize transcriptional changes induced by maternal diet in several adult tissues and to test whether differences in DNA methylation or microRNA expression could explain these changes.
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View Samples