Filters
Organism
Technology
Platform
SRP186329
Homo sapiens
407 Downloadable Samples
Illumina HiSeq 2500
Description
There is a growing need for fast and accurate methods for testing developmental neurotoxicity across industrial, pharmaceutical, and environmental chemical exposures. Current approaches, such as in vivo animal studies, and assays of animal and human primary cell cultures, suffer from challenges related to time, cost, and applicability to human physiology. Prior research demonstrated success employing machine learning to predict developmental neurotoxicity using gene expression data collected from complex human 3D tissue models exposed to various compounds, but the complexity of 3D tissue models require extensive expertise and effort to employ. While a 3D tissue model is more physiologically accurate, by focusing only on the goal of constructing an assay of developmental neurotoxicity, we propose that a simpler 2D tissue model may prove sufficient. We thus compared the accuracy of predictive models trained on data from a 2D tissue model with those trained on prior dataset from a more complex 3D tissue model, and found the accuracy of the 2D model to be substantially better than the 3D model. Furthermore, we found that the 2D tissue model is more robust and consistent under stringent gene set selection, whereas the 3D tissue model suffers substantial degradation of accuracy. While both approaches have advantages and disadvantages, we propose that our described 2D tissue model has the potential to serve as a valuable tool for decision makers when prioritizing neurotoxicity screening. Overall design: H1-NPC cells were thawed and expanded in DF3S+N2B27+5ng/ml FGF2 for 5 days before they were harvested by Accutase treatment. Roughly 1x10e5 cells were then seeded into one well of a 48 well plate in DF3S+N2B27. Chemical treatment started on the same day (day 0). Samples are collected at indicated time points by lysing cells directly on plate with 150ul RLT buffer. Chemical information can be found a separate sheet.
Publication Title
Machine learning to predict developmental neurotoxicity with high-throughput data from 2D bio-engineered tissues.
Alternate Accession IDs
Sample Metadata Fields
Cell line, Subject, Compound, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Knockdown of the transcription factor PU.1 (Spi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of PU.1 knockdown hematopoietic stem cells (HSC) in the preleukemic phase by linear amplification and genome-wide array analysis to identify transcriptional changes preceding malignant transformation. Hierarchical cluster analysis and principal component analysis clearly distinguished PU.1 knockdown from wildtype HSC. Jun family transcription factors c-Jun and JunB were among the top downregulated targets. Retroviral restoration of c-Jun expression in bone marrow cells of preleukemic mice partially rescued the PU.1-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to reduced clonogenic growth, loss of leukemic self-renewal capacity, and prevented leukemia in transplanted NOD-SCID mice. Examination of 305 AML patients confirmed the correlation between PU.1 and JunB downregulation and suggests its relevance in human disease. These results delineate a transcriptional pattern that precedes the leukemic transformation in PU.1 knockdown HSC and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1-induced AML by blocking differentiation (c-Jun) and increasing self-renewal (JunB). Therefore, examination of disturbed gene expression in HSC can identify genes whose dysregulation is essential for leukemic stem cell function and are targets for therapeutic interventions.
Publication Title
Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
In an effort to define unique and common signatures of NK cell activity that is non-detected at the protein level, we studied the entire transcriptome of NK cells.
Publication Title
Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Ewing sarcoma, an osteolytic malignancy that mainly affects children and young adults, is characterized
Publication Title
DKK2 mediates osteolysis, invasiveness, and metastatic spread in Ewing sarcoma.
Alternate Accession IDs
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The role of topographic cues in controlling commitment of induced pluripotent stem cells (iPSCs) is largely unknown. Here we demonstrate that groove-ridge nanostructures induce the elongation of iPSC colonies, guide the orientation of apical actin fibers and direct the polarity of cell division. Elongation of iPSC colonies impacts also on the intrinsic molecular patterning which seems to be orchestrated starting from the rim of the colonies. We followed the hypothesis that nanotopography directly modulates the transcriptional program of iPSC, further to guiding the overall spatial organization of the colonies. Single iPSC were seeded on flat (PI flat) and nanostructured polyimide (PI 650) and gene expression profiles were analyzed after three days. No significant differences were observed when cells were kept under culture conditions that sustained pluripotency. Then, we analyzed gene expression changes upon two weeks of multi-lineage differentiation. Many genes revealed significant expression changes in the course of differentiation and this was more pronounced on PI flat as compared to PI 650. Comparison of iPSC that were either differentiated on flat or nanostructured biomaterials revealed differential expression of several genes. Noteworthy, among significantly regulated genes, the biggest fold change on PI 650 versus PI flat after differentiation was observed in ANKRD1, which is one of the best readouts of YAP/TAZ activity. Our study suggests that nanotopography impacts on orientation and organization of iPSC colonies and highlight a possible interaction between mechanosensors and mechanotransducers.
Publication Title
Surface Topography Guides Morphology and Spatial Patterning of Induced Pluripotent Stem Cell Colonies.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Purpose: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols in the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their beneficial effects.
Publication Title
Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part, Cell line, Race
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We previously observed reduced graft survival for kidney transplants having interstitial fibrosis with subclinical inflammation, but not fibrosis alone, on 1-year protocol biopsy. The current study aimed to determine whether fibrosis with inflammation at 1 year is associated with renal functional decline in a low-risk transplant cohort and to characterize the nature of the inflammation. Subjects were living-donor, tacrolimus/mycophenolate-treated transplant recipients without overt risk factors for reduced graft survival (n=151). Transplants with normal histology (n=86) or fibrosis alone (n=45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, while those having fibrosis with inflammation (n=20) had declining glomerular filtration rate and reduced graft survival. Immunohistochemistry confirmed increased interstitial T-cells and macrophages/dendritic cells in the fibrosis with inflammation group. Gene expression was performed on a subset of biopsies in each group and demonstrated increased expression of transcripts related to innate and cognate immunity in transplants having fibrosis with inflammation. Pathway- and pathological process-specific analyses of microarray profiles revealed that, in fibrosis with inflammation, over-expressed transcripts were enriched for potentially damaging immunological activities including Toll-like receptor signaling, antigen presentation/dendritic cell maturation, interferon gamma-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes. Thus, fibrosis with inflammation in 1-year protocol biopsies is associated with reduced graft survival and function and with a rejection-like gene expression signature even in recipients with no clinical risk for inferior outcome. Early interventions aimed at altering rejection-like inflammation may favor improved long-term KTx survival.
Publication Title
Fibrosis with inflammation at one year predicts transplant functional decline.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- IlluminaHiSeq2500
Description
Although mechanisms of acquired resistance of EGFR mutant non-small cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here, we observe that acquired resistance caused by the T790M gatekeeper mutation can occur either by selection of pre-existing T790M clones or via genetic evolution of initially T790M-negative drug tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug tolerant cells had a diminished apoptotic response to third generation EGFR inhibitors that target T790M EGFR; treatment with navitoclax, an inhibitor of BCL-XL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug resistant cancer cells can both pre-exist and evolve from drug tolerant cells, and point to therapeutic opportunities to prevent or overcome resistance in the clinic. Overall design: Examination of mRNA levels of PC9 parental, drug-tolerant, PC9-GR2 and PC9-GR3 cells after treatment with vehicle, gefitinib or WZ4002 for 24 hours.
Publication Title
Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiles of normal kidney (3 technical replicates) and a renal tumor (3 technical replicates) from a hereditary leiomyomatosis and renal cell cancer (HLRCC) patient carrying a germline mutation in the fumarate hydratase (FH) gene.
Publication Title
Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-?) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-? bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-?/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-?/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system. Overall design: polyA RNA profiling of Neural Stem/Progenitor cells (NPCs) cultured in basal/Th1/Th2 conditions, of Exosomes derived from NPCs cultured in basal/Th1/Th2 conditions and of EVs derived from NPCs cultured in Basal/Th1/Th2 conditions. Total RNA was purified using Trizol. Purity and integrity were confirmed by BioAnalyser (Agilent). Paired End library construction and poly-A selection were performed by EASIH (The Eastern Sequence and Informatics Hub, University of Cambridge, Cambridge) according to the Illumina standard protocol. Sequencing was performed by EASIH using Illumina GAII.
Publication Title
Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples