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 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 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 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 SamplesThe use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI.
Identification of temporal and region-specific myocardial gene expression patterns in response to infarction in swine.
Sex, Specimen part, Treatment, Time
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 SamplesMutations altering the normal function of C/EBPa are frequent in acute myeloid leukaemia with normal karyotype. MYB, a cooperating partner of C/EBPa, is likewise heavily implicated in AML. Here we investigate how the relative requirement for the transcription factor MYB in AML relates to the particular combinations of wild type and mutated alleles of CEBPA. Through knockdown of Myb in murine cell lines modelling the spectrum of CEBPA mutations we show that the consequences of reduced Myb depend on the mutational status of Cebpa. Importantly, Myb knockdown fails to override the block in myeloid differentiation in cells with biallelic N-terminal C/EBPa mutations, demonstrating for the first time that the dependency on Myb observed in AML is much lower in leukaemia with this combination of mutations. By comparing genome-wide analyses of gene expression following Myb knockdown and ChIP-seq data for the binding of C/EBPa isoforms, we provide evidence for a functional cooperation between C/EBPa and Myb in the maintenance of the leukaemia state. This co-dependency breaks down when both alleles of CEBPA harbour N-terminal mutations, as a subset of C/EBPa-regulated genes only bind the short p30 C/EBPa isoform and, unlike other C/EBPa regulated genes, do so without a requirement for Myb. Overall design: Gene expression analysis of FMH9, KL and LL cells with and without Myb knockdown
Dependence on Myb expression is attenuated in myeloid leukaemia with N-terminal CEBPA mutations.
Subject
View SamplesAnalysis of knockdown of SDHD with or without knockdown of CDKN1C or SLC22A18 at gene expression level.
Parent-of-origin tumourigenesis is mediated by an essential imprinted modifier in SDHD-linked paragangliomas: SLC22A18 and CDKN1C are candidate tumour modifiers.
Specimen part, Cell line
View Samples