Skeletal muscles are formed in a variety of shapes and sizes, and this diversity impacts muscle function and disease susceptibility. To understand how muscle diversity is generated, we performed gene expression profiling of muscle subsets from Drosophila embryos. By comparing the transcriptional profiles of two muscle subsets, we identified a core group of founder cell-enriched genes. We screened mutant embryos for muscle defects and identified Sin3A and 10 other transcription and chromatin regulators as having novel functions in the Drosophila embryonic somatic musculature. Sin3A is required for the morphogenesis of a subset of muscles, and Sin3A mutants display muscle loss and misattachment. Additionally, misexpression of identity gene transcription factors in Sin3A heterozygous embryos leads to direct transformations of one muscle into another, while overexpression of Sin3A results in the reverse transformation. Our data implicate Sin3A as a key buffer controlling muscle responsiveness to transcription factors in the formation of muscle identity, thereby generating tissue diversity.
Whole-genome analysis of muscle founder cells implicates the chromatin regulator Sin3A in muscle identity.
Specimen part
View SamplesThe multiple claims about reactivation of the embryonic stem cell (ESC) pluripotency factor OCT4 in somatic cells are highly controversial due to the fact that there is no direct evidence that OCT4 has a functional role in cells other than ESCs. Herein we demonstrate that smooth muscle cell (SMC)-specific knockout of Oct4 within atherosclerotic mice resulted in increased lesion size and multiple changes consistent with decreased plaque stability. SMC-lineage tracing studies showed that lesions from SMC-specific conditional Oct4 KO mice had a reduced number of SMCs likely due to impaired SMC migration. RNA-seq analysis of lesion specimens showed that loss of Oct4 in SMCs was associated with marked activation of genes associated with inflammation and suppression of genes associated with cell migration, a number of which were shown to be activated in cultured SMCs by the combination of hypoxia and oxidized phospholipids in an OCT4-dependent manner. Activation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4 promoter and was HIF1a- and KLF4-dependent. Results provide the first genetic evidence that OCT4 plays a functional role in somatic cells and highlight the importance of further investigation of possible OCT4 functions in somatic cells. Overall design: In vivo: mRNA profiles of 18 week fed Western diet wild type (WT) and Oct4-/- mice were generated by deep sequencing, four animals per group, using Illumina HiSeq 2000. In vitro: a smooth muscle cell wild type (WT) and Oct4-/- (KO) primary aortic cell line was generated and used. mRNA profiles were generated by deep sequencing, in triplicates, using Illumina HiSeq 2000, for the following groups: WT-normoxia-vehicle; WT-normoxia-POVPC; KO-normoxia-vehicle; KO-normoxia-POVP; WT-hypoxia-vehicle; WT-hypoxia-POVPC; KO-hypoxia-vehicle; and KO-hypoxia-POVPC.
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis.
Specimen part, Cell line, Treatment, Subject
View SamplesTotal RNA sequenceing method was used to compare the differential expression of genes in HCT116 cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells Overall design: Examination of total RNA expressed after cells with vitamin C, 5-Aza-CdR and combination treatment compared to untreated cells
Vitamin C increases viral mimicry induced by 5-aza-2'-deoxycytidine.
No sample metadata fields
View SamplesObjective:
Gene expression analysis in absence epilepsy using a monozygotic twin design.
Sex
View SamplesUlcerative colitis (UC) and Crohns disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies. To identify pathogenic processes underlying these disease subtypes, using single endoscopic pinch biopsies to estabolish 36 expression profiles, we elucidated gene expression patterns of active and inactive areas of UC and CD, and compared these to infectious colitis and healthy controls.
Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis.
No sample metadata fields
View SamplesGene expression profiles were performed to compare the difference in sigmoid colon biopsies between from healthy control and patients with ulcerative colitis.
MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha.
No sample metadata fields
View SamplesCancer-specific changes in DNA methylation can alter genetic stability, genomic structure, and gene expression. Promoter CpG island methylation can result in transcriptional silencing and plays an important role in the oncogenic process. We used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Here, we describe the identification of novel groups of breast tumors characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating the existence of a breast-CpG island methylator phenotype (B-CIMP). B-CIMP imparts a distinct epigenomic profile and is a strong determinant of metastatic potential.
Breast cancer methylomes establish an epigenomic foundation for metastasis.
Specimen part
View SamplesWe evaluated transcriptional profiles in peripheral blood mononuclear cells (PBMCs) from 54 pregnant women in Kenya, 19 of whom delivered preterm.
Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The tumor suppressor Hic1 maintains chromosomal stability independent of Tp53.
No sample metadata fields
View SamplesWe hypothesised that genetic inactivation of the transcriptional repressor Hic1, would lead to changes in gene expression that may lead to transformation. We assessed changes in gene expression in pre-immortal MEF cell lines in which Hic1 was inactivated compared to controls.
The tumor suppressor Hic1 maintains chromosomal stability independent of Tp53.
No sample metadata fields
View Samples