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SRP015484
Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer IIx, Illumina Genome Analyzer II
Description
Both immunodeficient and wild type NOD mice exhibit defects in control of early T-cell development in the thymus. We show that Rag1-deficient NOD mice fail to enforce both the b-selection checkpoint and an earlier T-cell commitment checkpoint, based on genome-wide genetic and transcriptome analyses. A major QTL peak for the checkpoint breakthrough phenotype mapped to the diabetes susceptibility Idd9/11 region, as confirmed by congenic mouse analysis. Genome-wide RNA deep-sequencing revealed two classes of differences between NOD and B6 Rag1-deficient thymocytes: first, effects of genetic background prior to breakthrough, and second, effects of the breakthrough itself. These genotypes differentially express numerous signal transduction genes, prominently tyrosine kinase and actin-binding genes, some located within QTL regions. Emerging NOD breakthrough cells depart from the expected DN3 phenotype by expressing many stem cell-associated proto-oncogenes, such as Lmo2, Hhex, Lyl1, and Kit which are normally repressed earlier, and by illegitimate activation of post-b-selection genes like Cd2, Cd5, and Cd4. Co-expression of stem cell and T-cell genes persists in thymic lymphoma cells that emerge with high penetrance in these mice. These results imply that NOD thymocytes have defects that can collapse regulatory boundaries at two early T-cell checkpoints, which may predispose them to leukemia and autoimmunity. Overall design: Genetic and transcriptome analyses of early T-cell checkpoint failure and leukemia initiation in Rag1-deficient NOD mice
Publication Title
Loss of T cell progenitor checkpoint control underlies leukemia initiation in Rag1-deficient nonobese diabetic mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Unraveling the mechanisms underlying early neural differentiation of ESCs is crucial to the cell-based therapies of neurodegenerate diseases. Neural fate acquisition is proposed to be controlled by a default mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of embryonic stem cells (ESCs). Unexpectedly we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23-depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of other Mediator subunit, Med1 or Med15, did not alter the neural differentiation of ESCs; and Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23-depletion attenuated the BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1 that is involved in the Bmp4 promoter-enhancer communication. Interestingly, Med23 knockdown in zebrafish embryos also enhanced the neural development at early embryogenesis, which could be reversible by coinjection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination.
Publication Title
Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 3 Downloadable Samples
- Illumina HiSeq 4000
Description
DNA methylation on N6-adenine (6mA) has recently been found as a potentially new epigenetic mark in several unicellular and multicellular eukaryotes. However, its distribution patterns and potential functions in land plants, which are primary producers for most ecosystems, remain completely unknown. Here we report global profiling of 6mA sites at single-nucleotide resolution in the genome of Arabidopsis thaliana using single-molecule real-time sequencing. 6mA sites are widely distributed across the Arabidopsis genome and enriched over the pericentromeric heterochromatin regions. Nearly 30% of 6mA sites are present in gene bodies. Further analysis of 6mA methylome and RNA-sequencing data demonstrates that 6mA frequency positively correlates with the gene expression level in Arabidopsis. Consistently, histone variants associated with actively expressed genes interact with 6mA DNA. Our results uncover 6mA as a DNA mark associated with actively expressed genes in Arabidopsis, suggesting that 6mA serves as a novel epigenetic mark in land plants. Overall design: RNA-seq in 3-week-old Arabidopsis thaliana (Col-0) wild-type with three replicates.
Publication Title
DNA N<sup>6</sup>-Adenine Methylation in Arabidopsis thaliana.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Herein we compare mouse (C57B6/J background, 16 week old) adherent bone marrow stromal cell gene expression after 4 weeks of adipogenic differentiation in 3D versus 2D culture.
Publication Title
Development of a 3D bone marrow adipose tissue model.
Sample Metadata Fields
Sex, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BMP9 signaling has been implicated in hereditary hemorrhagic telangiectasia and vascular remodeling, acting via the HHT target genes, endoglin and ALK1. This study sought to identify endothelial BMP9-regulated proteins that could affect the HHT phenotype. Gene ontology analysis of cDNA microarray data obtained following BMP9 treatment of primary human endothelial cells indicated regulation of chemokine, adhesion, and inflammation pathways.
Publication Title
BMP9 regulates endoglin-dependent chemokine responses in endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We identified microRNA-188 differentially expressed in the BMSCs of aged and young mice and influenced on BMSCs differentiation with ageing.
Publication Title
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We identified microRNA-188 differentially expressed in the BMSCs of aged and young mice and influented on BMSCs differentiation with ageing.
Publication Title
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Illumina HiScanSQ
Description
Introduction: Though heavy alcohol drinking has been well characterized as causing a variety of injuries, recent epidemiological evidence in humans suggests moderate consumption may provide beneficial effects. For example, there exists a J- or U-shaped relationship between the level of alcohol intake and cardiovascular disease risk. We investigated the underlying mechanisms of these positive consequences by identifying which genes are responsive to moderate alcohol intake in the liver, the primary site for alcohol metabolism. Methods: Twelve female, inbred, alcohol-preferring (iP10a) rats were split equally between chronic water exposure and voluntary chronic ethanol exposure. Hepatic cholesterol and triglyceride levels were analyzed both histologically and biochemically. Hepatic transcriptomes were paired-end sequenced on the Illumina HiScanSQ system. Reads were analyzed and mapped using CLCbio Genomics Workbench 4.9. We confirmed altered expression of a subset of genes using TaqMan-based qRT-PCR. To quantify DNA methylation, we first digested DNA with methylation sensitive restriction enzymes and then performed qPCR using TaqMan assays surrounding the digest sites. Calculating ?Ct between a mock digest and digest determines the percent methylation in that locus. Results: Voluntary alcohol consumption in iP10a rats modeled moderate consumption in humans. These levels did not result in intrahepatic fat accumulation. Sequencing produced ~1.2 Gb of sequence per sample, and 65% of reads mapped uniquely. Using a FDR corrected p value of 0.05 we found 250 altered transcripts. Ontology analysis of genes with a fold change =1.3 identified many cholesterol synthesis genes and cytoskeleton subunit genes, all of which were down-regulated. Of the 28 genes reanalyzed by qRT-PCR, altered expression was confirmed in 24 genes including the majority of the cholesterol synthesis and cytoskeleton subunit genes. Lastly, we profiled methylation throughout the promoter and gene body of four genes elicited in the RNA-Seq experiment. We found that alcohol caused demethylation at all loci; however this loss happened in a site-specific, tightly regulated manner. Conclusion: Voluntary consumption in the iP10a animals models moderate consumption in humans, does not produce intrahepatic fat accumulation, and causes down-regulation of a majority of cholesterol synthesis genes. Moderate alcohol also results in a tightly-regulated demethylation effect. Our results explain, at least in part, the J- or U-shaped relationship between level of alcohol intake and cardiovascular disease risk. Overall design: We sequenced 12 female iP10a rat hepatic transcriptomes providing 6 biological replicates for water control and 6 for ethanol treatment.
Publication Title
A snapshot of the hepatic transcriptome: ad libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Human brain structure and size requires regulated division of neural stem cells (NSCs). NSCs undergo precise divisions to self-renew and to produce intermediate neural progenitors (INPs) and neurons. The factors that regulate NSC divisions remain poorly understood, as do mechanistic explanations of how aberrant NSC division causes reduced brain size, as seen in microcephaly. Here we demonstrate that Magoh, a component of the core exon junction complex (EJC) that binds spliced RNA, controls cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly due to INP depletion, neuronal apoptosis, and improper mitotic spindle orientation. Defective mitosis underlies these phenotypes as depletion of EJC components disrupts mitotic spindle integrity, chromosome number and genomic stability. We show that an essential function of Magoh is to regulate expression of the human microcephaly protein, LIS1, and that Lis1 addition rescues neurogenesis defects caused by Magoh knockdown, thus providing a genetic explanation for the microcephaly. This study uncovers new requirements for the EJC in brain development, NSC maintenance, mitosis and chromosome stability, thus implicating this complex in the pathogenesis of microcephaly.
Publication Title
The exon junction complex component Magoh controls brain size by regulating neural stem cell division.
Sample Metadata Fields
Specimen part
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