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SRP042249
Homo sapiens
36 Downloadable Samples
IlluminaHiSeq2000
Description
Cancer tissue-like structures were developed by using established human tumor cell lines in perfusion-based bioreactor systems. In colorectal cancer (CRC) cell lines, perfusion allowed more homogeneous scaffold seeding than tri-dimensional (3D) static cultures and significantly (13.7 fold, p<0.0001) higher proliferation. Resulting tissues exhibited morphology and phenotypes similar to xenografts generated in immunodeficient mice. Whole transcriptome analysis of 2D, 3D static and 3D perfusion cultures revealed the highest correlation between xenografts and 3D perfusion cultures (r=0.985). Clinically relevant concentrations of 5-FU, used in neo- and adjuvant CRC treatment, had no effect on numbers of HT-29 CRC cells cultured in 3D perfusion or xenografts, as compared with a 55.8% reduction in 2D cultures. Treatment induced apoptosis in 2D cultures, but only “nucleolar stress” in perfused cells and xenografts, consistent with partial responsiveness. In 3D perfusion cultures BCL-2, TRAF1, and FLIP gene expression was marginally affected, as compared with significant down-regulation in 2D cell cultures. Accordingly, ABT-199 BCL-2 inhibitor, induced cytostatic effects in 3D perfusion but not in 2D cell cultures (p=0.003). Tumor cells from partially responsive (Dworak 2) patients undergoing neo-adjuvant treatment, typically (10/11) expressed BCL-2, as compared with 0/3 highly (Dworak 3-4) responsive and 4/15 fully resistant CRC (Dworak 0/1, p=0.03), closely matching 3D perfusion cultures data. These results indicate that 3D perfusion cultures efficiently mimic phenotypic and functional features observed in xenografts and clinical specimens. These models may be of critical translational relevance to address fundamental human tumor cell biology issues and to develop predictive pre-clinical tests of novel compounds. Overall design: Expression profiles of colorectal cancer cell lines cultured in 2D, 3D static, 3D perfusion or growing as xenografts were generated by deep sequencing, in triplicates, using Illumina HiSeq2000.
Publication Title
Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed "in vivo".
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 16 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Increased ethanol intake, a major predictor for the development of alcohol use disorders, is facilitated by the development of tolerance to both the aversive and pleasurable effects of the drug. The molecular mechanisms underlying ethanol tolerance development are complex and are not yet well understood. To identify genetic mechanisms that contribute to ethanol tolerance, we examined the time course of gene expression changes elicited by a single sedating dose of ethanol in Drosophila.
Publication Title
Ethanol-regulated genes that contribute to ethanol sensitivity and rapid tolerance in Drosophila.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Long-term exposure of MCF-7 breast cancer cells to ethanol stimulates oncogenic features.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used a whole genome approach to identify major functional gene categories (including xenobiotic transporters and metabolizing enzymes) whose expression depends on gestational age. STUDY DESIGN: We compared gene expression profiles of 1st (45-59 days) and 2nd trimester (109-115 days), and C-section term placentae. RESULTS: In 1st trimester placentae, genes related to cell cycle, DNA, aminoacids and carbohydrate metabolism were significantly overrepresented, while genes related to signal transduction were downregulated. In the organism defense category, we identified genes involved in chemical response, metabolism, and transport. Analysis of signal transduction pathways suggested, and subsequently confirmed independently, that the Wnt pathway was regulated by gestational age. CONCLUSIONS: Our study will serve as a reference database to gain insight into the regulation of gene expression in the developing placentae and, thus, allow comparisons with placentae from complicated pregnancies such as those in women experiencing gestational diabetes, pre-eclampsia and teratogenic sequelae.
Publication Title
Profiling gene expression in human placentae of different gestational ages: an OPRU Network and UW SCOR Study.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 90 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Knowing the gene expression profiles of drug-metabolizing enzymes and transporters throughout gestation is important for understanding the mechanisms of pregnancy-induced changes in drug pharmacokinetics. In this study, we compared gene expression of drug-metabolizing enzymes and transporters in the maternal liver, kidney, small intestine, and placenta of pregnant mice throughout gestation by microarray analysis. Specifically, we investigated cytochrome P450 (Cyp), UDP-glucuronosyltranserase (Ugt), and sulfotransferase (Sult), as well as ATP-binding cassette (Abc) and solute carrier (Slc) transporters. We found that relatively few Ugt and Sult genes were impacted by pregnancy in maternal tissues and placenta. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 in the liver were down-regulated, with the greatest changes occurring on gestation days (gd) 15 and 19 compared to non-pregnant controls (gd 0). However, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. Cyp expression in mid-gestation placenta (gd 10 and 15) was generally greater than that in term placenta (gd 19). There were also notable changes in Abc and Slc transporters. Abcc3 in the liver was down-regulated by 60%, and Abcb1a, Abcc4, and Slco4c1 in the kidney were down-regulated by 30-60% on gd 15 and 19 versus gd 0. Abcc5 in the placenta was induced 3-fold on gd 10 versus gd 15 and 19, whereas Slc22a3 expression in the placenta on gd 10 was 90% lower than that on gd 15 and 19. Overall, this study demonstrates important gestational age-dependent expression of drug-metabolizing enzymes and transporter genes, which may have mechanistic relevance to human pregnancy.
Publication Title
Gestational age-dependent changes in gene expression of metabolic enzymes and transporters in pregnant mice.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The Drosophila gene dLmo encodes a transcriptional regulator involved in wing development and behavioral responses to cocaine and ethanol.
Publication Title
An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 246 Downloadable Samples
- NextSeq 500
Description
Recent advances in single-cell transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. Here, we utilized massively parallel single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally-distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune cell deficiencies within prkdcD3612fs, il2rgaY91fs and double homozygous mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types including two classes of natural killer immune cells, classically-defined and erythroid-primed hematopoietic stem and progenitor cells, mucin secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first comprehensive single cell transcriptomic analysis of kidney and marrow cells in the adult zebrafish. Overall design: The goal of our study is to establish the transcriptional profiles of hematopoietic and kidney cell lineages residing in the zebrafish whole kidney marrow. Firstly, we performed single-cell RNA sequencing by a modified Smart-seq2 protocol on sorted single cells from fluorescent transgenic zebrafish lines, which label distinct blood cell types (n = 246 cells total). Secondly, we utilized droplet-based single-cell RNA sequencing (inDrop) to investigate unmarked, comprehensive hematopoietic lineage structure within wild-type, casper-strain zebrafish (N=3 animals, n=3,782 cells total). From this, we identified ten distinct hematopoietic groups of blood and immune identities. Thirdly, we confirmed blood lineage interpretations by comparing hematopoietic lineages within wild-type fish with mutant zebrafish with known immunodeficiencies, including prkdc(D3612fs) (N=3 animals, n=3,201 cells), il2rga(Y91fs) (N=2 animals, n=2,068 cells) and prkdc(D3612fs), il2rga(Y91fs) double compound mutant fish (N=2 animals, n=2,276 cells). Lastly, we identified seven structural and functional cell lineages of kidney identities in the whole kidney marrow (n=1,699 kidney cells).
Publication Title
Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Recent advances in single-cell transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. Here, we utilized massively parallel single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally-distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune cell deficiencies within prkdcD3612fs, il2rgaY91fs and double homozygous mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types including two classes of natural killer immune cells, classically-defined and erythroid-primed hematopoietic stem and progenitor cells, mucin secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first comprehensive single cell transcriptomic analysis of kidney and marrow cells in the adult zebrafish. Overall design: The goal of our study is to establish the transcriptional profiles of hematopoietic and kidney cell lineages residing in the zebrafish whole kidney marrow. Firstly, we performed single-cell RNA sequencing by a modified Smart-seq2 protocol on sorted single cells from fluorescent transgenic zebrafish lines, which label distinct blood cell types (n = 246 cells total). Secondly, we utilized droplet-based single-cell RNA sequencing (inDrop) to investigate unmarked, comprehensive hematopoietic lineage structure within wild-type, casper-strain zebrafish (N=3 animals, n=3,782 cells total). From this, we identified ten distinct hematopoietic groups of blood and immune identities. Thirdly, we confirmed blood lineage interpretations by comparing hematopoietic lineages within wild-type fish with mutant zebrafish with known immunodeficiencies, including prkdc(D3612fs) (N=3 animals, n=3,201 cells), il2rga(Y91fs) (N=2 animals, n=2,068 cells) and prkdc(D3612fs), il2rga(Y91fs) double compound mutant fish (N=2 animals, n=2,276 cells). Lastly, we identified seven structural and functional cell lineages of kidney identities in the whole kidney marrow (n=1,699 kidney cells).
Publication Title
Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Description
Many cancers are postulated to harbor developmental hierarchies in which cells display variability in stem-like character, tumor propagating ability, and proliferation. In glioblastoma (GBM), glioma stem cells (GSCs) reside atop such a tumor cellular hierarchy, and are thought to resist current therapies and thus underlie inevitable relapse. Here we show that GSCs can evade RTK inhibition by reversibly regressing to a slow-cycling state reminiscent of quiescent neural stem cells. This process involves up-regulation of numerous histone demethylases, including KDM6A/B, which remodel the chromatin landscape and are selectively essential for drug persister survival. Chromatin remodeling is accompanied by activation of various neurodevelopmental master regulators and Notch signaling, changes which closely parallel critical aspects of neural stem cell biology. Thus our findings illustrate how cancer cells may hijack native developmental programs for deranged proliferation, adaptation, and tolerance in the face of stress. Our studies highlight key roles for chromatin remodeling and developmental plasticity in GBM biology, and suggest strategies for overcoming therapeutic resistance by targeting epigenetic and developmental pathways. Overall design: ChIP-seq for histone modifications and Notch factors in glioblastoma stem cell lines with various drug treatments RNA-seq in glioblastoma stem cell lines with various drug treatments
Publication Title
Adaptive Chromatin Remodeling Drives Glioblastoma Stem Cell Plasticity and Drug Tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer with Reduced Representation Bisulfite Sequencing. DNMT-inhibition by 5-Azacytidine at low concentrations reverted the pro-metastatic phenotype. 5-Azacytidine led to preferential loss of DNA methylation at sites that were DNA hypermethylated during the in vivo selection. Changes in DNA methylation persisted over time.
Publication Title
DNA methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting polycomb target genes.
Sample Metadata Fields
Cell line
View Samples