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GSE72204
Homo sapiens
15 Downloadable Samples
Illumina HiSeq 2500, Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st), Illumina HiSeq 2500
Description
Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared to tissue-specific progenitors. Direct interrogation of iron uptake demonstrated CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin - two core iron regulators - to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, and on which CSCs have an epigenetically programmed, targetable dependence.
Publication Title
Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared to tissue-specific progenitors. Direct interrogation of iron uptake demonstrated CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin - two core iron regulators - to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, and on which CSCs have an epigenetically programmed, targetable dependence. Overall design: RNA-seq of primary patient-derived GBM cancer stem cells and normal human neural progenitor cells
Publication Title
Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2500
Description
Glioblastoma ranks as one of the most lethal human cancers, with no effective therapies. To discover novel therapeutic targets, here we performed parallel in vivo and in vitro RNA interference screens of epigenetic regulators and show that transcription elongation factors are essential for human glioblastoma cell survival in vivo, but not in vitro. Context-specific dependency in vivo is driven by microenvironment-induced global changes in the cancer epigenome. JMJD6, a top in vivo-specific hit, binds at enhancers and correlates with increased transcription of known pause-controlled genes. JMJD6 knockdown in patient-derived glioblastoma cells enhances survival of mice bearing orthotopic tumors. Moreover, elevated levels of JMJD6 alone, as well as transcription elongation factors collectively, informs tumor grade and predicts poor prognosis for patients. Our work provides a rationale for targeting transcription elongation as a therapeutic strategy in glioblastoma and, more broadly, the power of in vivo phenotypic screening to identify therapeutically relevant targets in cancer. Overall design: RNA-seq of primary patient-derived GBM cells grown in in vivo tumor microenvironment or in vitro in serum free cell culture
Publication Title
Transcription elongation factors represent in vivo cancer dependencies in glioblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 4 Downloadable Samples
Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
During embryogenesis, the pancreas develops from separate dorsal and ventral buds, which fuse to form the mature pancreas. Little is known about the functional differences between these two buds or the relative contribution of cells derived from each portion to the pancreas after fusion. To follow the fate of dorsal or ventral bud derived cells in the pancreas after fusion, we produced chimeric Elas-GFP transgenic/wild type embryos in which either dorsal or ventral pancreatic bud cells expressed GFP. We found that ventral pancreatic cells migrate extensively into the dorsal pancreas after fusion, whereas the converse does not occur. Moreover, we found that annular pancreatic tissue is composed exclusively of ventral pancreas derived cells. To identify ventral pancreas specific genes that may play a role in pancreatic bud fusion, we isolated individual dorsal and ventral pancreatic buds, prior to fusion, from stage 38/39 Xenopus laevis tadpoles and compared their gene expression profiles. Morpholino-mediated knockdown of one of these ventral specific genes, transmembrane 4 superfamily member 3 (tm4sf3), inhibited dorsal-ventral pancreatic bud fusion as well as acinar cell differentiation. Conversely, overexpression of tm4sf3 promoted the development of annular pancreas. Our results are the first to define molecular and behavioral differences between the dorsal and ventral pancreas, and suggest an unexpected role for the ventral pancreas in pancreatic bud fusion.
Publication Title
The tetraspanin Tm4sf3 is localized to the ventral pancreas and regulates fusion of the dorsal and ventral pancreatic buds.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 8 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Ngn3 is a master regulator of pancreatic endocrine development. It is necessary for the creation of all endocrine cells in mice. Little is known about the genes that act downstream of the transcription factor Ngn3 in pancreas endocrine development to specify each of the endocrine lineages. As a consequence, little is known about the genes involved in early development and the specification of the beta cell. We used microarrays to identify Ngn3 downstream genes that are involved in early and ectopic beta cell development in Xenopus laevis. We overexpressed Ngn3 in the Xenopus early endoderm and analyzed the genes that are upregulated four hours after.
Publication Title
Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Xenopus laevis
- 18 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Recently a new neonatal diabetes syndrome, Mitchell-Riley syndrome, was discovered. To identify the genetic cause of the syndrome homozygosity mapping was used, several chromosomal regions were linked to Mitchell-Riley syndrome. In situ hybridization of genes from one such region using model organism Xenopus laevis identified RFX6 as a potential candidate gene; mutant forms of RFX6 were subsequently found in Mitchell-Riley patients. Analysis of the expression pattern of RFX6 in Xenopus development shows it is expressed broadly in the endoderm early in development, and later RFX6 becomes restricted to the endocrine cells of the gut and pancreas. Morpholino knockdown of RFX6 in Xenopus caused a loss of pancreas marker gene expression. Injection of exogenous wild type RFX6 rescued the morpholino phenotype in Xenopus tadpoles. Attempts to rescue the loss-of-function phenotype using mutant forms of RFX6 found in Mitchell-Riley patients were unsuccessful suggesting the changes lead to loss-of-function and could be the cause of Mitchell-Riley syndrome. Microarray analysis of gene expression in knockdown tissue suggested a downregulation in marker genes for lung, stomach and heart, ambiguous results for the liver, and an upregulation in kidney marker gene expression. RT-PCR and in situ hybridization confirms a loss of lung, stomach and heart gene expression, no change in liver marker hex and an upregulation in kidney marker KcnJ1. The fact that the morpholino phenotype affects multiple organs suggests that RFX6 has a broad role early in endoderm development.
Publication Title
Functional analysis of Rfx6 and mutant variants associated with neonatal diabetes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Our study in zebrafish is the first to use an animal model to understand the biology of the developmental disorder Roberts Syndrome (RBS). RBS is caused by mutations in the ESCO2 gene.
Publication Title
A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To further understand the differences occurring in MCF10A cells as they polarize and differentiate in the Transwell model, we performed gene expression profiling with Affymetrix Human Genome U133 Plus 2.0 Arrays. Four experimental time points, were sampled: conventional cultures of MCF10A cells grown on plastic (Monolayer) and MCF10A cells plated on Transwells sampled at three TEER values, 200-300 cm2 (Base), 1400-1600 cm2 (Midpoint), and 3000-3200 cm2 (Plateau).
Publication Title
In vitro multipotent differentiation and barrier function of a human mammary epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples