This SuperSeries is composed of the SubSeries listed below.
Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.
Specimen part, Disease
View SamplesThere is a distinct signature of differentially expressed probes from diagnosis to relapse
Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.
Specimen part, Disease
View SamplesGene expression profiling (GEP) can reveal characteristic signatures associated with distinct biologic subtypes of acute lymphoblastic leukemia (ALL).
Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles.
Specimen part, Disease
View SamplesPatients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have distinct clinical and biological features. Whereas most DS-ALL cases lack the sentinel cytogenetic lesions that guide risk assignment in childhood ALL, JAK2 mutations and CRLF2 overexpression are highly enriched. To further characterize the unique biology of DS-ALL, we performed genome-wide profiling of 58 DS-ALL and 35 non-Down syndrome (NDS) ALL cases by DNA copy number, loss of heterozygosity, gene expression, and methylation analyses. We report novel deletions within the 6p22 histone gene cluster as significantly more frequent in DS-ALL, occurring in 12 DS (24%) and only a single NDS case (3%) (Fishers exact p = 0.013). Homozygous deletions yielded significantly lower histone expression levels, and were associated with higher methylation levels, distinct spatial localization of methylated promoters, and enrichment of highly methylated genes for specific pathways and transcription factor binding motifs. Gene expression profiling identified CRLF2 overexpression in nearly half DS-ALL cases, and supervised analysis identified an associated 39-gene signature. However, no expression signature was identified for DS-ALL overall, nor for histone status, suggesting that DS-ALL constitutes several, heterogeneous molecular entities. Characterization of pathways associated with histone deletions and high CRLF2 expression may identify opportunities for novel targeted interventions.
Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
Treatment
View SamplesLeishmania major infected human dendritic cells (DCs) exhibit a marked induction of IL-12 ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity. In this study, we utilized Affymetrix Genechips to globally assess the host cell genes and pathways associated with L. major infection during early infection (2, 4, 8, and 24 hrs) in human myeloid-derived DCs. Bioinformatic analyses of the hybridized microarray chips identified 728 genes, represented by 848 unique probe sets, which, when compared to uninfected samples were observed to be significantly differentially expressed by one-way ANOVA. Altogether, the data provide a genome-wide perspective on the transcriptional influences Leishmania species exert within human DCs during early infection, and provides a platform for further investigations toward functionally characterizing candidate genes of importance to the IL-12 based immune response to infections.
Human dendritic cells exhibit a pronounced type I IFN signature following Leishmania major infection that is required for IL-12 induction.
Specimen part, Time
View SamplesThe role of the histone mehyltrasferase G9a (also known as Ehmt2) in cardiac hypertrophy has not been studied extensively. To address how G9a promotes cardiac hypertrophy, we assessed the gene expression signature defined by G9a in cardiomyocytes (CM) of mice subject to transverse aortic constriction (TAC) for 1 wk, a surgical procedure that causes cardiac hypertrophy following the induction of pressure overload. To this end, we compared the expression profiles of CMs isolated from mice treated with the G9a inhibitor BIX-01294 and control groups (untreated and DMSO-treated mice at baseline and after TAC). The expression profiles were defined by Illumina arrays .
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
No sample metadata fields
View SamplesThe role of the histone mehyltrasferase G9a (also known as Ehmt2) in heart has not been extensively studied. To identify the genes regulated by G9a in the normal heart, we first generated a conditional, cardiac-specific KO mouse for this gene using the Cre-Lox approach, crossing G9a flox/flox mice with aMHC-MerCreMer mice (Cre mice were used as controls). Then, we sequenced total RNA (Total-RNA-seq) from cardiomyocyte-enriched populations isolated from G9a-KO and Cre mice, and compared the two expression profiles. Overall design: Profiling of the transcriptome of cardiomyocyte-enriched populations isolated from G9a-KO and Cre mice. Two biological replicates were profiled for each cell type.
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
Cell line, Subject
View SamplesProfiling of the transcriptome of FITChigh/FSCdim and FITCdim/FSChigh sub-populations. Three biological replicates were profiled for each cell type. Overall design: Profiling of the transcriptome of FITChigh/FSCdim and FITCdim/FSChigh sub-populations. Three biological replicates were profiled for each cell type.
An autofluorescence-based method for the isolation of highly purified ventricular cardiomyocytes.
Specimen part, Cell line, Subject
View SamplesMethylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC) – 5-mC's oxidation product – is unknown in the context of the heart. Here, we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks gene bodies of highly expressed genes and distal regulatory regions with enhanced activity. Pathological hypertrophy is characterized by a partial shift towards a fetal-like distribution pattern. We further demonstrate a regulatory function of TET2 and provide evidence that the expression of key cardiac genes, such as Myh7 is modulated by TET2-mediated 5-hmC deposition on the gene body and at enhancers in cardiac cells. We thus provide the first genome-wide analysis of 5-hmC in the cardiomyocyte, and establish the role of this epigenetic modification in heart development and disease Overall design: Profiling of the transcriptome of embryonic, neonatal, adult, 1 week hypertrophic cardiomyocytes, sh-control and sh-TET2 cardiomyocytes. Two biological replicates were profiled for each cell type.
DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy.
Specimen part, Cell line, Subject
View Samples