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GSE66766
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Branched-chain amino acids (BCAA) have emerged as predictors of type 2 diabetes (T2D). However, their potential role in the pathogenesis of insulin resistance and T2D remains unclear. By integrating data from skeletal muscle gene expression and metabolomic analyses, we demonstrate evidence for perturbation in BCAA metabolism and fatty acid oxidation in skeletal muscle from insulin-resistant humans. Experimental modulation of BCAA flux in cultured cells alters fatty acid oxidation in parallel. Furthermore, heterozygosity for the BCAA metabolic enzyme methylmalonyl-CoA mutase (MUT) alters muscle lipid metabolism in vivo, resulting in increased muscle triacylglycerol (TAG) accumulation and increased body weight after high-fat feeding. Together, our results demonstrate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by reducing fatty acid oxidation and increasing TAG accumulation.
Publication Title
Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global transcriptome patterns were performed using ORE1-IOE-2h (2h after Estradiol and Mock treatment) as well as transiently (6h) overexpressed Arabidopsis mesophyll cell protoplasts
Publication Title
NAC transcription factor ORE1 and senescence-induced BIFUNCTIONAL NUCLEASE1 (BFN1) constitute a regulatory cascade in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 96 Downloadable Samples
Illumina HiSeq 2500
Description
Stranded, single-end, polyA+, transcriptional profiles were created from ovaries of sterile and fertile sov heteroallelic mutants and Gal4 driven sov RNAi knockdowns. Overall design: 15 ovaries from 4-5 day old post-eclosion females grown in uncrowded conditions were dissected and pooled for each biological replicate for a total of three replicates per genotype. Total RNA was extracted from tissues and polyA RNA was isolated and used to prepare stranded RNAseq libraries. 50 bp single-end sequencing was performed and mapped to Drosophila melanogaster release 6.21 genome.
Publication Title
<i>Drosophila</i> Heterochromatin Stabilization Requires the Zinc-Finger Protein Small Ovary.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alternative mRNA splicing provides transcript diversity and has been proposed to contribute to several human diseases. Here, we demonstrate that expression of genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. To determine the metabolic impact of reduced splicing factor expression, we further evaluated the splicing factor, SFRS10, identified as down-regulated in obese human liver and skeletal muscle and in high fat fed rodents. siRNA-mediated reductions in SFRS10 expression induced lipogenesis and lipid accumulation in cultured hepatocytes. Moreover, SFRS10 heterozygous mice have both increased hepatic lipogenic gene expression and hypertriglyceridemia. We also demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10, with reduced SFRS10 levels favoring the lipogenic isoform of LPIN1. Importantly, LPIN1-specific siRNA abolished the lipogenic effects of decreased SFRS10 expression. Together, our results indicate reduced expression of SFRS10 alters LPIN1 splicing and induces lipogenesis, demonstrating that reduced splicing factor expression observed in human tissues may contribute to metabolic phenotypes associated with human obesity.
Publication Title
Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis.
Sample Metadata Fields
Age, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMf, CD11cloMf are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMf and CD11cloMf increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways Overall design: CD11chiMf Sham, n=3; CD11chiMf RAS, n=4; CD11cloMf Sham, n=3; CD11cloMf RAS, n=4; KRM Sham, n=4; KRM RAS, n=3;
Publication Title
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PDE4 inhibitors, which activate cAMP signaling by reducing cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic leukemia (CLL) cells but not normal human T cells. The explanation for such differential sensitivity remains unknown. Here, we report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T and B cells.
Publication Title
Chronic lymphocytic leukemia and B and T cells differ in their response to cyclic nucleotide phosphodiesterase inhibitors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Long-term pharmacological glucocorticoid therapy causes atrophy and hypofunction of the adrenal cortex. Following glucocorticoids withdrawal, a functional and anatomic regeneration take place, whose cellular and molecular mechanisms are poorly understood
Publication Title
Sonic Hedgehog and WNT Signaling Promote Adrenal Gland Regeneration in Male Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- IlluminaHiSeq2500
Description
The goal of this study is to compare the transcriptome of the 2 MVT1 subpopulations in order to identify new genes and pathways that stands beyond the CD24+ aggressive phenotype Overall design: mRNA profiles of CD24- and CD24+ cells were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500
Publication Title
Deep sequencing of mRNA in CD24(-) and CD24(+) mammary carcinoma Mvt1 cell line.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.
Publication Title
Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 52 Downloadable Samples
- Illumina HiSeq 2500
Description
We report the correlation between lung-derived neonatal MSCs and 2 clinical variables among preterm newborns: corrected gestational age (CGA) at collection and the severity of bronchopulmonary dysplasia (BPD) Overall design: To test the correlation between the transcriptional profiles of tracheal aspirate-derived mesenchymal stromal cells with late stage lung development and with bronchopulmonary dysplasia.
Publication Title
Lung-Resident Mesenchymal Stromal Cells Reveal Transcriptional Dynamics of Lung Development in Preterm Infants.
Sample Metadata Fields
Specimen part, Subject
View Samples