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GSE38031
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine ES-derived neural stem cells (NSC) were not irradiated (ctrl) or irradiated with 10Gy and cultured for 7 days (irr).
Publication Title
DNA damage in mammalian neural stem cells leads to astrocytic differentiation mediated by BMP2 signaling through JAK-STAT.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sox2 is expressed by neural stem and progenitor cells, and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors.
Publication Title
Prospective identification, isolation, and profiling of a telomerase-expressing subpopulation of human neural stem cells, using sox2 enhancer-directed fluorescence-activated cell sorting.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 3 Downloadable Samples
IlluminaGenomeAnalyzer
Description
Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented “hyper-angiogenesis” defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin-dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis. Overall design: Identification of endothelial-expressed microRNA from FACS-isolated zebrafish endothelial cells.
Publication Title
miR-221 is required for endothelial tip cell behaviors during vascular development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Using Tbx18Cre to target embryonic DP precursors, we ablate Sox2 early and efficiently, resulting in diminished hair shaft outgrowth. Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased Bmp inhibitor Sostdc1, a direct Sox2 transcriptional target.
Publication Title
Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
The histological grade of carcinomas describes the ability of tumor cells to organize differentiated epithelial structures and has prognostic impact. Molecular control of differentiation in normal and cancer cells relies on lineage-determining transcription factors (TFs) that activate the repertoire of cis-regulatory elements controlling cell type-specific transcriptional outputs. TF recruitment to cognate genomic DNA binding sites results in the deposition of histone marks characteristic of enhancers and other cis-regulatory elements. Here we integrated transcriptomics and genome-wide analysis of chromatin marks in human pancreatic ductal adenocarcinoma (PDAC) cells of different grade to identify first, and then experimentally validate the sequence-specific TFs controlling grade-specific gene expression. We identified a core set of TFs with a pervasive binding to the enhancer repertoire characteristic of differentiated PDACs and controlling different modules of the epithelial gene expression program. Defining the regulatory networks that control the maintenance of epithelial differentiation of PDAC cells will help determine the molecular basis of PDAC heterogeneity and progression. Overall design: Poly(A) fraction of the total RNA from human pancreatic ductal adenocarcinoma cell lines was extracted and subjected to by multiparallel sequencing. Experiments were carried out in unmodified cells in duplicate, genome edited clonal CFPAC1 cells (2 KLF5-deleted CRISPR-Cas9 clones, 3 ELF3-deleted CRISPR-Cas9 clones and 2 wt clones) and CFPAC1 cells ectopically expressing ZEB1 or empty vector control (in duplicate).
Publication Title
Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
During normal or pathological epithelial-to-mesenchymal transition, epithelium-specific gene expression is shut down, with the DNA-binding factor ZEB1 acting as a master suppressor of epithelial identity. Here, we show that ZEB1 occupies primate-specific tandem repeats (TRs) harboring dozens of copies of its DNA-binding motif and located within genomic loci relevant for epithelial identity. Deletion of one such repeat in a quasi-mesenchymal human cancer cell line induced the reacquisition of epithelial features and phenocopied the effects of ZEB1 gene deletion. Since ZEB1 binds clustered motifs in a non-cooperative manner, changes in its nuclear concentration enable graded adjustments of TR occupancy, thus fine-tuning repression level. In addition, high motif density in TRs allows ZEB1 binding (and shutdown of epithelial programs) despite differences in chromatin organization and accessibility among epithelial cell types. Overall design: Total RNA from human pancreatic ductal adenocarcinoma cell lines was processed for multiparallel sequencing. Experiments were carried out in genome edited clonal MiaPaCa2 cells (3 ZEB1-deleted CRISPR-Cas9 clones and 3 wt clones).
Publication Title
Co-optation of Tandem DNA Repeats for the Maintenance of Mesenchymal Identity.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Dissection of melanoma heterogeneity through gene expression profiling has led to the identification of two major phenotypes, conventionally defined as MITF high / proliferative and AXL high / invasive. Tumors or single melanoma cells characterized by a predominant AXL-related gene program show enhanced expression of sets of genes involved in motility, invasion and regulation of epithelial-mesenchymal transition (EMT), while these genes are downregulated in tumors or cells with a predominant MITF-related gene program. The activation of the AXLhi/MITFlo invasive gene program in melanoma is characterized by aberrant expression of transcription factors (TFs) involved in the embryonic EMT process. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Here we provide evidence for a new actionable pathway that controls melanoma EMT-like/invasive phenotype. We show that in MITFlo melanomas, the TF NFATc2 controls the EMT-like transcriptional program, the invasive ability of neoplastic cells, as well as in-vitro and in-vivo growth, through a pathway that functionally links c-myc to FOXM1 and EZH2. Targeting of NFATc2, FOXM1 or EZH2 inhibited melanoma migratory and invasive activity. Moreover, pharmacological co-targeting of NFATc2 and EZH2 promoted apoptosis of BRAF-mutant melanomas with intrinsic resistance to BRAF inhibition.
Publication Title
An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Therapeutic targeting of BRAFV600E has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. In fact MAPK and PI3K/mTOR signaling pathways are constituively activated in most cancers, including melanoma, to sustain the melanoma growth/survival. A large panel of melanoma were characterized for resistance/susceptibility to different inhibitors targeting MAPK and PI3K/mTOR signaling pathways and the synergistic effect of combinatorial treatments affecting both pathways. These effects were evaluated in terms of cell viability (MTT), apoptosis (Annexin V-PI), caspase 3/7 activity and subG1 cell fraction, highlighting a hierarchy in the combination effects. Further, a smaller panel of melanoma cell lines, were treated with inhibitors singularly and in combination to test the effects on the expression of principal proteins involved in these two pathways. Gene expression profile was performed to analyse the gene modulation induced by inhibitors to identify new strategies to fight melanoma resistance.
Publication Title
Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
We report the application of single-molecule-based sequencing technology for high-throughput profiling of NSC transcriptome. Overall design: Wild type and Sox2-deleted NSC were sequenced; three independent samples from wild type, and three from Sox2-deleted brains (different individual mice).
Publication Title
Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 85 Downloadable Samples
- Illumina HiSeq 2000
Description
We generated genome-wide RNASeq data from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and methylation data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma. Overall design: examination of genome-wide genome-wide gene expression levels and comparison to phenotypes
Publication Title
DNA methylation in lung cells is associated with asthma endotypes and genetic risk.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples