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Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Induced pluripotent stem cell-derived human hepatocyte-like cells (iHeps) could provide a powerful tool for studying the mechanisms underlying human liver development and disease, testing the efficacy and safety of pharmaceuticals across different patients (i.e. personalized medicine), and enabling cell-based therapies in the clinic. However, current in vitro protocols that rely upon growth factors and extracellular matrices (ECM) alone yield iHeps with low levels of liver functions relative to adult primary human hepatocytes (PHHs). Moreover, these low hepatic functions in iHeps are difficult to maintain for prolonged times (weeks to months) in culture. Here, we engineered a micropatterned co-culture (iMPCC) platform in a multi-well format that, in contrast to conventional confluent cultures, significantly enhanced the functional maturation and longevity of iHeps in culture for 4 weeks in vitro when benchmarked against multiple donors of PHHs. In particular, iHeps were micropatterned onto collagen-coated domains of empirically optimized dimensions, surrounded by 3T3-J2 murine embryonic fibroblasts, and then sandwiched with a thin layer of ECM gel (Matrigel). We assessed iHep maturity via global gene expression profiles, hepatic polarity, secretion of albumin and urea, basal CYP450 activities, phase-II conjugation, drug-mediated CYP450 induction, and drug-induced hepatotoxicity. Conclusion: Controlling both homotypic interactions between iHeps and heterotypic interactions with stromal fibroblasts significantly matures iHep functions and maintains them for several weeks in culture. In the future, iMPCCs could prove useful for drug screening, studying molecular mechanisms underlying iHep differentiation, modeling liver diseases, and integration into human-on-a-chip systems being designed to assess multi-organ responses to compounds.
Publication Title
Enhancing the functional maturity of induced pluripotent stem cell-derived human hepatocytes by controlled presentation of cell-cell interactions in vitro.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Sustained Ca2+ entry into CD4+CD8+ double-positive thymocytes is required for positive selection. We identified a voltage-gated Na+ channel (VGSC), essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited sustained Ca2+ influx induced by positive-selecting ligands and in vitro positive selection of CD4+ but not CD8+ T cells. In vivo shRNA knockdown of Scn5a specifically inhibited positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, directly demonstrating VGSC expression was responsible for increased sensitivity. Thus active VGSCs in thymocytes provides a mechanism by which a weak positive selecting signal can induce sustained Ca2+ signals required for CD4+ T cell development.
Publication Title
A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations affecting the RAS-MAPK pathway frequently occur in relapse neuroblastoma tumors, which suggests that activation of this pathway is associated with a more aggressive phenotype. To explore this hypothesis we generated several model systems to define a neuroblastoma RAS-MAPK pathway signature. We could show that activation of this pathway in primary tumors indeed correlates with poor survival and is associated with known activating mutations in ALK and other RAS-MAPK pathway genes. From integrative analysis we could show that mutations in PHOX2B, CIC and DMD are also associated with an activated RAS-MAPK pathway. Mutation of PHOX2B and deletion of CIC in neuroblastoma cell lines induces activation of the RAS-MAPK pathway. This activation was independent of phosphorylated ERK in the CIC knock out systems. Furthermore, deletion of CIC causes a significant increase in tumor growth in vivo. These results show that the RAS-MAPK pathway is involved in tumor progression, and establish CIC as a powerful tumor suppressor that functions downstream of this pathway in neuroblastoma.
Publication Title
RAS-MAPK Pathway-Driven Tumor Progression Is Associated with Loss of CIC and Other Genomic Aberrations in Neuroblastoma.
Sample Metadata Fields
Cell line
View Samples
GSE2473- Arabidopsis thaliana
- 44 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Inflorescence stages 1 to 12 from mutants involved in Arabidopsis small RNA metabolism. Three biological replicates of each mutant comprising at least 9 independent plants were harvested, and the expression profiles were determined using Affymetrix ATH1 arrays. Comparisons among the sample groups allow the identification of genes regulated by small RNAs (microRNAs and siRNAs).
Publication Title
microRNA-directed phasing during trans-acting siRNA biogenesis in plants.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
T helper cell subsets have unique calcium (Ca2+) signals when activated with identical stimuli. The regulation of these Ca2+ signals and their correlation to the biological function of each T cell subset remains unclear. Trpm4 is a Ca2+-activated cation channel that we found is expressed at higher levels in Th2 cells compared to Th1 cells. Inhibition of Trpm4 expression increased Ca2+ influx and oscillatory levels in Th2 cells and decreased influx and oscillations in Th1 cells. This inhibition of Trpm4 expression also significantly altered T cell cytokine production and motility. Our experiments revealed that decreasing Trpm4 levels divergently regulates nuclear localization of NFAT. Consistent with this, gene profiling did not show Trpm4 dependent transcriptional regulation and T-bet and GATA-3 levels remain identical. Thus, Trpm4 is expressed at different levels on T helper cells and plays a distinctive role in T cell function by differentially regulating Ca2+ signaling and NFAT localization.
Publication Title
Trpm4 differentially regulates Th1 and Th2 function by altering calcium signaling and NFAT localization.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The primary aim of this study was to evaluate the changes in hepatocyte gene expression under short-term hypoxic conditions in wild type and HIF-1a null cultures. To this end, hypoxia treated cultures were subjected to incubation with 1% O2/5% CO2/94% N2 at 37 C for eight hours prior to RNA isolation. Duplicate normoxic controls were established from separate animals wherein cultures were untreated and treated with Adbgal. Biological triplicates of wild type and HIF-1a null cultures were placed under hypoxic conditions and subsequently processed for microarray analysis. A total of 10 microarray hybridizations were performed.
Publication Title
In vitro liver tissue model established from transgenic mice: role of HIF-1alpha on hypoxic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogen-responsive genes were identified by transcript profiling of estrogen-treated MCF-7 breast cancer cells.
Publication Title
Identification of functional networks of estrogen- and c-Myc-responsive genes and their relationship to response to tamoxifen therapy in breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5 we made an inducible Elf5 sh-RNA knock down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin-induction of Elf5 expression tempered the anti-proliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
Publication Title
The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5.
Sample Metadata Fields
Disease, Cell line, Treatment
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
MYB-bHLH-TTG1 regulates Arabidopsis seed coat biosynthesis pathways directly and indirectly via multiple tiers of transcription factors
Publication Title
MYB-bHLH-TTG1 Regulates Arabidopsis Seed Coat Biosynthesis Pathways Directly and Indirectly via Multiple Tiers of Transcription Factors.
Sample Metadata Fields
Specimen part
View Samples