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Homo sapiens
72 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oxidized phospholipids are thought to promote atherogenesis by stimulating endothelial cells (ECs) to produce inflammatory cytokines, such as IL-8. In studies with mouse models, we previously demonstrated that genetic variation in inflammatory responses of endothelial cells to oxidized lipids contributes importantly to atherosclerosis susceptibility. We now show that similar variations occur in cultured aortic ECs derived from multiple heart transplant donors. These variations were stably maintained between passages and, thus, reflect either genetic or epigenetic regulatory differences. Expression array analysis of aortic EC cultures derived from 12 individuals revealed that >1,000 genes were regulated by oxidized phospholipids. We have used the observed variations in the sampled population to construct a gene coexpression network comprised of 15 modules of highly connected genes. We show that several identified modules are significantly enriched in genes for known pathways and confirm a module enriched for unfolded protein response (UPR) genes using siRNA and the UPR inducer tunicamycin. On the basis of the constructed network, we predicted that a gene of unknown function (MGC4504) present in the UPR module is a target for UPR transcriptional activator ATF4. Our data also indicate that IL-8 is present in the UPR module and is regulated, in part, by the UPR. We validate these by using siRNA. In conclusion, we show that interindividual variability can be used to group genes into pathways and predict gene-gene regulatory relationships, thus identifying targets potentially involved in susceptibility to common diseases such as atherosclerosis.
Publication Title
Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process, and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative datasets that can be leveraged to explore post-transcriptional and post-translational processes that are essential for mitochondrial adaptation.
Publication Title
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We recently reported the scalable in vitro production of functional stem cell-derived cells. Here we extend this approach to generate SC- cells from Type 1 diabetic patients (T1D), a cell type that is destroyed during disease progression and has not been possible to extensively study. These cells express cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice, and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of cell stress. Using these assays, we find no major differences in T1D SC- cells compared to SC- cells derived from non-diabetic patients (ND). These results show that T1D SC- cells can be used for the treatment of diabetes, drug screening, and the study of cell biology.
Publication Title
Generation of stem cell-derived β-cells from patients with type 1 diabetes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Pcyt2 defient mice has metabolic syndrome and insulin resistance. We used microarray to study the gene expression of these mice to
Publication Title
Male-Specific Cardiac Dysfunction in CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)-Deficient Mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Two human acute lymphoblastic leukemia cell lines (Molt-4 and CCRF-CEM) were treated with direct (A-769662) and indirect (AICAR) AMPK activators. Molt-4 and CCRF-CEM cells were obtained from ATCC (CRL-1582 and CCL-119). Control samples were used for the analysis of metabolic differences between cell lines. Therefore the data was analyzed in combination with, metabolomic data, and the genome-scale reconstruction of human metabolism. For experiments cells were grown in serum-free medium containing DMSO (0.67%) at a cell concentration of 5 x 105 cells/mL.
Publication Title
Prediction of intracellular metabolic states from extracellular metabolomic data.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MLL1 WT or KO MEF with and without HSP90 inhibitor treatment
Publication Title
Identification of mixed lineage leukemia 1(MLL1) protein as a coactivator of heat shock factor 1(HSF1) protein in response to heat shock protein 90 (HSP90) inhibition.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The generation of insulin-producing pancreatic cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide cells. Here we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive cells from hPSC in vitro. These stem cell derived cells (SC) express markers found in mature cells, flux Ca2+ in response to glucose, package insulin into secretory granules and secrete quantities of insulin comparable to adult cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice.
Publication Title
Generation of functional human pancreatic β cells in vitro.
Sample Metadata Fields
Specimen part, Cell line
View Samples
SRP162295- Mus musculus
- 18 Downloadable Samples
Illumina HiSeq 2500
Description
Mus musculus transcriptome during infection with Candida albicans strains SC5314 and 101
Publication Title
Persistence of <i>Candida albicans</i> in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 72 Downloadable Samples
- NextSeq 500
Description
In vitro differentiation of human stem cells can produce pancreatic beta cells, the insulin-secreting cell type whose loss underlies Type 1 Diabetes. As a step towards mastery of this process, we report on transcriptional profiling of >100,000 individual cells sampled during in vitro beta cell differentiation and describe the cells that emerge. We resolve populations corresponding to beta cells, alpha-like poly-hormonal cells, non-endocrine cells that resemble pancreatic exocrine cells and a previously unreported population resembling enterochromaffin cells. We show that the beta and alpha-like cells are stable for weeks in culture without exogenous growth factors and that gene expression changes associated with in vivo beta cell maturation are recapitulated in vitro. We demonstrate that stem-cell derived enterochromaffin cells can synthesize and secrete serotonin in vitro. To remove exocrine cells, we characterize a scalable re-aggregation technique that efficiently selects endocrine cells. Finally, we use a high-resolution sequencing time course to characterize gene expression dynamics during human pancreatic endocrine induction from which we develop a lineage model of in vitro beta cell differentiation. This study provides a deeper perspective on the current state of human stem cell differentiation and is a jumping-off point for future endeavors in in vitro differentiation of pancreatic islet cells and their application in regenerative medicine. Overall design: Single-cell mRNA sequencing of pluripotent stem cells differentiating in vitro towards pancreatic beta cells. The data & metadata match the initial submission of the manuscript, not the final version.
Publication Title
Charting cellular identity during human in vitro β-cell differentiation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
To identify the role of the SH3PXD2A-HTRA1 fusion on gene expression in Schwann cells
Publication Title
The genomic landscape of schwannoma.
Sample Metadata Fields
Specimen part
View Samples