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GSE75789
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to such treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and -5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased of cell proliferation, and increased cell cycle arrest and apoptosis in comparison to only irradiated cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation and cell cycle regulation. To our knowledge, this is the first study to describe role of miR-338-5p in GBM and its potential to improve sensitivity of GBM to radiation.
Publication Title
MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
RRF-3 and ERI-1 are first identified proteins required for accumulation of at least some endogenous secondary siRNAs in C.elegans. Genome wide gene expression analysis was performed on L4 stage rrf-3 and eri-1 mutant C. elegans to study effects caused by loss of these proteins. Mutant rrf-3 and eri-1 strains exhibited similar expression patterns when compared to N2 wild type, while 72 transcripts were found to be co-overexpressed and 4 transcripts co-underexpressed (> 2-fold, p< 0.05). Ontology analysis indicated many of the gene products were associated with protein phosphorylation and sperm function. These results provide additional support for the hypothesis that RRF-3 and ERI-1 act together in a siRNA pathway and may indicate biological processes that are related to endo-siRNAs.
Publication Title
Whole genome microarray analysis of C. elegans rrf-3 and eri-1 mutants.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of different iPSC clones in comparison to parental fibroblasts and Pluripotent ESC and iPSC lines
Publication Title
CD44 is a negative cell surface marker for pluripotent stem cell identification during human fibroblast reprogramming.
Sample Metadata Fields
Cell line
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- Caenorhabditis elegans
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
The aryl hydrocarbon receptor (AHR) functions in higher organisims in development, metabolism and toxic responses. Its Caenorhabditis elegans (C. elegans) ortholog, AHR-1, facilitates neuronal development, growth and movement. We investigated the effect of AHR mutation on the transcriptional profile of L4 stage C. elegans using RNA-seq and quantitative real-time PCR in order to understand better AHR-1 function at the genomic level. Illumina HiSeq 2000 sequencing yielded 51.1, 61.2 and 54.0 million reads from wild-type controls, ahr-1(ia03) and ahr-1(ju145) mutants, respectively, providing detection of over 18,000 transcripts in each sample. Fourteen transcripts were over-expressed and 125 under-expressed in both ahr-1 mutants when compared to wild-type. Under-expressed genes included soluble guanylate cyclase (gcy) family genes, some of which were previously demonstrated to be regulated by AHR-1. A neuropeptide-like protein gene, nlp-20, and an F-box domain protein gene fbxa-192 and its pseudogenes fbxa-191 and fbxa-193 were also under-expressed. Conserved xenobiotic response elements were identified in the 5'' flanking regions of some but not all of the gcy, nlp-20 and fbxa genes. These results extend previous studies demonstrating control of gcy family gene expression by AHR-1, and furthermore suggest a role of AHR-1 in regulation of a neuropeptide gene as well as pseudogenes. Overall design: One sample was created from each of the following strains: wild-type N2, ahr-1(ia03) mutant and ahr-1(ju145) mutant. In data analysis, each mutant sample was individually compared to the wild-type sample to find differentially expressed genes.
Publication Title
Transcriptional profiling reveals differential expression of a neuropeptide-like protein and pseudogenes in aryl hydrocarbon receptor-1 mutant Caenorhabditis elegans.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcription factor and microRNA interactions in lung cells: an inhibitory link between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cell-specific gene expression is achieved by a combination of mechanisms including transcriptional and post-transcriptional regulation. The transcription factor Nkx2-1, essential for lung cell differentiation, mainly acts in transcriptional activation but can directly or indirectly repress gene expression. microRNAs are a class of small non-coding RNA that control one of the major mechanisms of gene repression. To identify miRNAs regulated by Nkx2-1 that may mediate its repressing effects, we knocked-down Nkx2-1 in mouse lung epithelial cell lines and systematically identified targets by genome-wide miR and mRNA expression analyses. Nkx2-1 controls expression of miRs known to contribute to lung cell differentiation in development and disease and others not previously described. Amongst the significantly altered miRs, the mir-106a-363 cluster, miR-1195, miR-378, and miR-346 are directly correlated with the levels of Nkx2-1, whereas miR-200c/b, miR-221, and miR- 222 are inversely correlated. These miRNAs are expressed in embryonic lung at day E11.5, and/or E19.5 determined by in-situ hybridization. Expression of predicted targets of mir-1195, mir-346 and miR-200c and mir-221/222 were evaluated by mRNA expression microarrays in Nkx2-1 knockdown cells identifying those anti-correlated to the corresponding miRNA expression. Genes regulated by mir-1195, Cyp2s1 and Map3k2, by mir-346, Klf6, and miR-200c, Myb, Nfib, and Six1, were validated by qRT-PCR. Inhibition of mir-1195 confirms the inverse correlation of this miRNA with its putative targets Cyp2s1 and Map3k2. This miRNA-mRNA expression analysis identifies potential paths of Nkx2-1 mediated gene repression, and contributes to the understanding of gene regulation in lung epithelial differentiation and development.
Publication Title
Transcription factor and microRNA interactions in lung cells: an inhibitory link between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 69 Downloadable Samples
- NextSeq 500
Description
The rapid improvements in single cell sequencing technologies and analyses methods afford greater scope for dissecting organoid cultures composed of multiple cell types and create an opportunity to interrogate these models to understand tissue biology, cellular behaviour and interactions. To this end, retinal organoids generated from human embryonic stem cells (hESCs) were analysed by single cell RNA-Sequencing at three time points of differentiation. Combinatorial data from all time points revealed the presence of nine clusters, five of which corresponded to key retinal cell types, namely retinal pigment epithelium (RPE), retinal ganglion cells (RGCs), cone and rod photoreceptors and Müller glia cells. The remaining four clusters expressed genes typical of mitotic cells, extracellular matrix (ECM) components and those involved in retinal homeostasis. The cell clustering analysis revealed the decreasing presence of mitotic cells and RGCs, formation of a distinct RPE cluster, the emergence of cone and rod photoreceptors from photoreceptor precursors and an increasing number of Müller Glia cells over time. The pseudotime analysis resembled the order of cell birth during retinal development, with the mitotic cluster commencing the trajectory and the large majority of Müller glia being the latest. Together, these data demonstrate the feasibility and potential of single cell RNA-Seq to dissect the inherent complexity of the organoids and the orderly birth of key retinal cell types. Overall design: A hESC (H9) cell line harbouring a CRX-GFP reporter was differentiated to retinal organoids 25. Samples were collected at 60, 90 and 200 days, dissociated, partitioned into single cells using the Fluidigm C1 Single-Cell mRNA-Seq HT IFC and processed for scRNA-Seq.
Publication Title
Deconstructing Retinal Organoids: Single Cell RNA-Seq Reveals the Cellular Components of Human Pluripotent Stem Cell-Derived Retina.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Transgenic C. elegans strains that express human SUMO-1 under the control of pan-neuronal (aex-3) or pan muscular (myo-4) promoters were assayed for gene expression changes.
Publication Title
Overexpression of SUMO perturbs the growth and development of Caenorhabditis elegans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here we present genome-wide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs available for future exploration. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator Eomes. We used catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the Eomes locus in vivo, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development. Overall design: Gene expression profile of mouse purified neuroepithelial cells (NECs) was generated by RNA-seq. --------------- This represents the RNA-Seq component only
Publication Title
Epigenome profiling and editing of neocortical progenitor cells during development.
Sample Metadata Fields
Specimen part, Subject
View Samples