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GSE25752
Rattus norvegicus
4 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Ischemia, fibrosis, and remodeling lead to heart failure after severe myocardial infarction (MI). Myoblast sheet transplantation is a promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in this detrimental disease. We hypothesized that in a rat model of MI-induced chronic heart failure this therapy could further be improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF) in the myoblast sheets. We studied the ability of wild type (L6-WT) and human HGF-expressing (L6-HGF) L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression using microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD) ligation and allowed heart failure to develop for four weeks. Thereafter, we administered L6-WT (n=15) or L6-HGF (n=16) myoblast sheet therapy. Control rats (n=13) underwent LAD ligation and rethoracotomy without therapy and five rats underwent sham-operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy administration. We analyzed cardiac angiogenesis and left ventricular architecture from histological sections 4 weeks after therapy. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further enhanced by hHGF-expression.
Publication Title
hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure.
Sample Metadata Fields
No sample metadata fields
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- 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- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
The retinal pigment epithelial (RPE) cell line ARPE-19 provides a widely-used alternative to native RPE. However, retention of the native RPE phenotype becomes problematic after multiple passages. We wished to determine if suitable culture conditions and differentiation could restore RPE-appropriate gene expression to ARPE-19. ARPE-19 cells at passages p9 to p12, grown in DMEM containing high glucose and pyruvate with 1% fetal bovine serum, were differentiated for up to 4 months. Using RNA-Seq, we compared the transcriptome of ARPE-19 cells kept in long-term culture with those cultured for 4 days. The 4 month cells developed the classic native RPE phenotype with heavy pigmentation. RNA-Seq analysis provided a comprehensive view of the relative abundance and differential expression of genes in the 4 month cells. Of the 16,757 genes with detectable signals, nearly 2435 genes were upregulated, and 931 genes were down-regulated with a fold change differences of 2 or more. Genes characteristic of RPE, including RPE65, RDH5 and RDH10, were greatly increased in ARPE-19 cells maintained at confluence for 4 months. Comparison with microarray data sets from human primary cell lines revealed important overall similarities in expression of "signature" genes. The results of this study demonstrate that ARPE-19 cells can express genes specific to native human RPE cells when appropriately cultured, and thus, can provide a relevant system to study differentiated cellular functions of RPE in vitro. Overall design: RNA-Seq profiles of ARPE-19 cells grown for 4 days or 4 months; triplicate replicates were sequenced.
Publication Title
Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples