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SRP173814
Homo sapiens
4 Downloadable Samples
Illumina HiSeq 2500
Description
Although human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) have emerged as a novel platform for heart regeneration, disease modeling, and drug screening, their immaturity significantly hinders their application. A hallmark of postnatal cardiomyocyte maturation is the metabolic substrate switch from glucose to fatty acids. We hypothesized that fatty acid supplementation would enhance hPSC-CM maturation. Fatty acid treatment induces cardiomyocyte hypertrophy and significantly increases cardiomyocyte force production. The improvement in force generation is accompanied by enhanced calcium transient peak height and kinetics, and by increased action potential upstroke velocity. Fatty acids enhance mitochondrial respiratory reserve capacity. RNA sequencing showed fatty acid treatment upregulates genes involved in fatty acid ß-oxidation and downregulates genes in lipid synthesis. Signal pathway analyses reveal that fatty acid treatment results in phosphorylation of multiple intracellular kinases. Thus, fatty acids increase human cardiomyocyte hypertrophy, force generation, calcium dynamics, action potential upstroke velocity, and oxidative capacity. This enhanced maturation should facilitate hPSC-CMs usage for cell therapy, disease modeling, and drug/toxicity screens. Overall design: We did RNA-seq of hPSC-CM culture in control and fatty acid media, with two biological replicates per condition
Publication Title
Fatty Acids Enhance the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Ion Torrent Proton
Description
This study shows that the TLR4/MyD88 pathway in intestinal mesenchymal cells promotes intestinal carcinogenesis in the APCmin mouse model. Overall design: 3' RNA-Seq (QuantSeq) profiling of ColVIcre+ wt and MyD88 knockout primary mouse intestinal mesenchymal cells before and after treatment with LPS for 6 hours. 3 replicates per group.
Publication Title
Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Triticum aestivum
- 35 Downloadable Samples
Affymetrix Wheat Genome Array (wheat)
Description
The wheat gene Lr34 confers partial resistance to all races of Puccinia triticina, the causal agent of wheat leaf rust. However, the biological basis for the exceptional durability of Lr34 is unclear. The Affymetrix wheat genome array was used to identify wheat genes differentially expressed in a compatible interaction (Tc), an R-gene mediated incompatible interaction (Tc-Lr1), and a race non-specific resistance interaction (Tc-Lr34) in response to infection challenge by P. triticina race 1 at anthesis. Transcriptome interrogation was conducted by comparing mock- and P. triticina-inoculated leaves harvested at 3 and 7 days post inoculation (dpi).
Publication Title
Lr34-mediated leaf rust resistance in wheat: transcript profiling reveals a high energetic demand supported by transient recruitment of multiple metabolic pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Comparison of Total RNA and Polysome-bound RNA populations in deltaTOR containing cells and control cells upon hepatocyitc differentiation.
Publication Title
Mammalian target of rapamycin activation impairs hepatocytic differentiation and targets genes moderating lipid homeostasis and hepatocellular growth.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The statsitcal model, latent pathway identification analysis (LPIA), was implemented for the analysis of A549 lung carcinoma cells treated with geldanamycin. Control and treated samples were assayed with Affymetrix HG_U133_plus_2 arrays and analyzed using LPIA. LPIA looks for statistically signcant evidence of dysregulation in a network of pathways constructed in a manner that explicitly links pathways through their common function in the cell. Geldanamycin (geld) is known to inhibit the molecular chaperone protein, Hsp90, and plays a role in preventing the malignant transformation and proliferation of healthy cells during oncogenesis. LPIA successfully identified pathways specific to geldanamycin effects at the gene transcription level.
Publication Title
Network-based prediction for sources of transcriptional dysregulation using latent pathway identification analysis.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The ubiquitously expressed G-protein-coupled receptor kinase 2 (GRK2, ADRBK1) is an indispensable kinase involved in growth, differentiation and development. Exaggerated GRK2 activity plays a major pathophysiological role in the development of cardiovascular diseases such as heart failure and hypertension. GRK2 exerts its functions by kinase-dependent and kinase-independent effects. To assess the differential impact of GRK2 on cellular signalling we established HEK cell clones with over-expression of comparable protein levels of GRK2 or the kinase-deficient GRK2-K220R mutant, respectively. HEK cells were either cultured in vitro or expanded in vivo, in immunodeficient NOD.Scid mice to discriminate between in vitro and in vivo effects of GRK2. Whole genome microarray gene expression profiling was performed of cultured HEK cells and of NOD.Scid mouse-expanded HEK clones. As an additional control, cells were re-cultured in vitro after expansion in NOD.Scid mice.
Publication Title
Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 12 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Intracranial aneurysms tend to form at bifurcation apices, where flow impingement causes high frictional force (or wall shear stress, WSS) and flow acceleration and deceleration that create positive and negative streamwise gradients in WSS (WSSG), respectively. In vivo, intracranial aneurysms initiate under high WSS and positive WSSG. Little is known about the responses of endothelial cells (ECs) to either positive or negative WSSG under high WSS conditions. We used cDNA microarrays to profile EC gene expression exposed to positive WSSG vs. negative WSSG for 24 hours in a flow chamber with converging and diverging channels, respectively. WSS varied between 3.5 and 28.4 Pa in each gradient channel. GO and biological pathway analysis indicated that positive WSSG favored proliferation, apoptosis, and extracellular matrix processing while decreasing expression of pro-inflammatory genes. A subset of characteristic genes was validated using qPCR: Genes for ADAMTS1, CKAP2 and NCEH1 had higher expression under positive WSSG compared to negative WSSG while TAGLN, THBS1, VCAM1, CCL2, and CSF2 had lower expression. To determine if these patterns of expression are also exhibited in vivo, we tested whether the extracellular matrix related protein ADAMTS1 and proliferation were modulated by positive WSSG during intracranial aneurysm initiation. An aneurysm was induced at the basiliar terminus in rabbits by bilateral carotid ligation. WSSG at the bifurcation was determined by computational fluid dynamic simulations from 3D angiography and mapped on immunofluorescence staining for ADAMTS1 and the proliferation marker, Ki-67. Endothelial ADAMTS1 protein and Ki-67 were significantly higher in regions with positive WSSG compared to adjacent sites where WSSG was negative. Our results indicate that WSSG can elicit distinct gene expression profiles in ECs. Increased matrix processing and high levels of proliferation under positive WSSG could contribute to intracranial aneurysm initiation by causing transient gaps in the endothelium or disrupting EC signals to smooth muscle cells.
Publication Title
Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hi CX3CR1hi (CD11b+CD103-) cells account for 80% of mouse colonic lamina propria (cLP) MHC-IIhi cells. Both CD11c+ and CD11c- cells within this population were identified as MPs based on multiple criteria, including a MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs, based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1-CD11b- DCs, CD103+CX3CR1-CD11b+ DCs and CD103-CX3CR1intCD11b+ DCs. In non-inflammatory conditions, Ly6Chi monocytes differentiated primarily into CD11c+, but not CD11c- MPs. In contrast, during colitis, Ly6Chi monocytes massively invaded the colon and differentiated into pro-inflammatory CD103-CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS and TNF. These findings demonstrate the dual capacity of Ly6Chi blood monocytes to differentiate into either regulatory MPs or inflammatory DCs in the colon, and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions.
Publication Title
Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Chronic high flow can induce arterial remodeling, and this effect is mediated by endothelial cells (ECs) responding to wall shear stress (WSS). To assess how WSS above physiological normal levels affects ECs, we used DNA microarrays to profile EC gene expression under various flow conditions. Cultured bovine aortic ECs were exposed to no flow (0 Pa), normal WSS (2 Pa) and very high WSS (10 Pa) for 24 hrs. Very high WSS induced a distinct expression profile when compared to both no flow and normal WSS. Gene ontology and biological pathway analysis revealed that high WSS modulated gene expression in ways that promote an anti-coagulant, anti-inflammatory, proliferative and pro-matrix remodeling phenotype. A subset of characteristic genes was validated using quantitative polymerase chain reaction (qPCR): Very high WSS upregulated ADAMTS1, PLAU (uPA), PLAT (tPA) and TIMP3, all of which are involved in extracellular matrix processing, with PLAT and PLAU also contributing to fibrinolysis. Downregulated genes included chemokines CXCL5 and IL-8 and the adhesive glycoprotein THBS1 (TSP1). Expressions of ADAMTS1 and uPA proteins were assessed by immunhistochemistry in rabbit basilar arteries experiencing increased flow after bilaterial carotid artery ligation. Both proteins were significantly increased when WSS was elevated compared to sham control animals. Our results indicate that very high WSS elicits a unique transcriptional profile in ECs that favors particular cell functions and pathways that are important in vessel homeostasis under increased flow. In addition, we identify specific molecular targets that are likely to contribute to adaptive remodeling under elevated flow conditions.
Publication Title
Endothelial cells express a unique transcriptional profile under very high wall shear stress known to induce expansive arterial remodeling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Raf kinase inhibitor protein (RKIP) is a dual inhibitor of the Raf kinase and the G-protein-coupled receptor kinase 2 (GRK2). GRK2 is an indispensable kinase, which exerts a major role in the pathogenesis of heart failure, and inhibition of GRK2 is cardioprotective in experimental models of heart failure. To investigate the cardiac function of RKIP as GRK2 inhibitor, we generated transgenic mice with myocardium-specific expression of RKIP under control of the alpha-MHC promoter. For comparison, mice with myocardium-specific expression of a GRK-specific peptide inhibitor (GRK-Inh) were also generated. Two different transgenic mouse models were established. Transgenic RKIP mice and transgenic GRK-Inh mice were born at Mendelian frequencey and grew to adulthood normally.
Publication Title
Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples