Human diffuse intrinsic pontine gliomas (DIPG) are an aggressive form of pediatric brain tumors that arise in the pons in young children thus resulting in significant morbidity and very poor survival. Recent data suggest that mutations in the histone H3.3 variant are often found in these tumors, though the mechanism of their contribution to oncogenesis remains to be elucidated. Here we report that the combination of constitutive PDGFRA activation and p53 suppression as well as expression of the K27M mutant form of the histone H3.3 variant leads to neoplastic transformation of hPSC-derived neural precursors. Our study demonstrates that human ES cells represent an excellent platform for the modeling of human tumors in vitro and in vivo, which could potentially lead to the elucidation of the molecular mechanisms underlying neoplastic transformation and the identification of novel therapeutic targets.
Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.
Specimen part
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PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Specimen part, Cell line
View SamplesThe role of PGC1alpha in breast cancer lung metastasis is largely unknown. We used expression data from lung metastasis of mice injected with PGC1alpha overexpression or control cells to understand global changes that occur upon overexpression of PGC1alpha that lead to lung metastasis.
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Specimen part, Cell line
View SamplesThe role of PGC1alpha in breast cancer lung metastasis is largely unknown. We used expression data from lung metastatic explants overexpressing PGC1alpha or control, treated with phenformin to understand global gene expression changes which occur in a PGC1alpha context and under phenformin treatment.
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Specimen part, Cell line
View SamplesTo understand global expression changes in a knockdown of PGC1alpha (siPGC1alpha) vs control (siControl) in a lung metastatic cell line (4175)
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Cell line
View SamplesBackground: Personalized medicine is predicated on the notion that individual biochemical and genomic profiles are relatively constant in times of good health and to some extent predictive of disease or therapeutic response. We report a pilot study quantifying gene expression and methylation profile consistency over time, addressing the reasons for individual uniqueness, and its relation to N=1 phenotypes. Methods: Whole blood samples from 4 African American women, 4 Caucasian women, and 4 Caucasian men drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays. Standard regression approaches were used to evaluate the proportion of variance for each type of omic measure that is among individuals, and to quantify correlations among measures and with clinical attributes related to wellness. Results: Longitudinal omic profiles are in general highly consistent over time, with an average of 67% of the variance in transcript abundance, 42% of CpG methylation level (but 88% for the most differentiated CpG per gene), and 50% of miRNA abundance among individuals, which are all comparable to 74% of the variance among individuals for 74 clinical traits. One third of the variance can be attributed to differential blood cell type abundance, which is also fairly stable over time, and a lesser amount to eQTL effects, whereas seven conserved axes of covariance that capture diverse aspects of immune function explain over half of the variance. These axes also explain a considerable proportion of individually extreme transcript abundance, namely approximately 100 genes that are significantly up- or down-regulated in each person and are in some cases enriched for relevant gene activities that plausibly associate with clinical attributes. A similar fraction of genes have individually divergent methylation levels, but these do not overlap with the transcripts, and fewer than 20% of genes have significantly correlated methylation and gene expression. Conclusions: People express an “omic personality” consisting of peripheral blood transcriptional and epigenetic profiles that are constant over the course of a year and reflect various types of immune activity. Baseline genomic profiles can provide a window into the molecular basis of traits that might be useful for explaining medical conditions or guiding personalized health decisions. Overall design: Whole blood samples from 12 subjects drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays.
Omic personality: implications of stable transcript and methylation profiles for personalized medicine.
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View SamplesMutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Ovarian cancer risk can be decreased by risk-reducing salpingo-oophorectomy (RRSO). Studies on RRSO material have altered the paradigm of serous ovarian cancer pathogenesis.
Microarray analysis of differentially expressed genes in ovarian and fallopian tube epithelium from risk-reducing salpingo-oophorectomies.
Specimen part, Subject
View SamplesThe transcriptomic profiles of mouse embryonic fibroblasts (MEFs) were investigated using the next-generation RNA sequencing (RNA-Seq). The CLC Genomic Workbench software was used to screen the differentially expressed transcripts. A total of 49 genes with a significantly differential expression (false discovery rate (FDR) p<0.05, fold change >2) in the female group as compared with the male group. Overall design: mRNA profiles of mouse embryonic fibroblast (MEF) were generated by RNA sequencing using the NextSeq 500 (Illumina).
KDM5D-mediated H3K4 demethylation is required for sexually dimorphic gene expression in mouse embryonic fibroblasts.
Sex, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Glioblastoma stem-like cells give rise to tumour endothelium.
Sex, Age, Specimen part
View SamplesTranscriptome analysis of RNAs from brain tumor
Glioblastoma stem-like cells give rise to tumour endothelium.
Sex, Age, Specimen part
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