In order to determine the imprinted transcription factor Zac1 targets, we overexpressed Zac1 in a mouse insulinoma cell line and measured the regulated expressed genes by RNA-seq. We have shown that Zac1 regulates many genes belonging to the Imprinted Gene Network, including genes coding for the extra-cellular matrix. Overall design: Determination of Zac1 target genes in transfected Min6 cells (4 biological replicates) using RNA-seq, .
Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network.
Specimen part, Subject
View SamplesIn vitro differentiation of embryonic stem cells (ESC) provides models that reproduce in vivo development and cells for therapy. Whether the epigenetic signatures that are crucial for brain development and function and that are sensitive to in vitro culture are similar between native brain tissues and their artificial counterpart generated from ESC is largely unknown. Here, using RNA-seq we have compared the parental origin-dependent expression of imprinted genes (IGs), a model of epigenetic regulation, in cerebral cortex generated either in vivo, or from ESCs using in vitro corticogenesis, a model that reproduces the landmarks of in vivo corticogenesis. For a majority of IGs, the expressed parental alleles were the same for in vivo and in vitro cortex. In most cases, this choice was already set in ESCs and faithfully maintained during the 3 weeks of in vitro corticogenesis. Confirming these findings, methylation, which selects the parental allele to be transcribed, was also largely equivalent between the 2 types of cortex and ESCs. Our results thus indicate that the allele specific expression of imprinted transcripts, a model of epigenetic regulation resulting from a differential methylation of parental genomes, is mostly mimicked in cortical cells derived from ESC. Overall design: We have crossed two strains of mice (B6 and JF1) that display more than 12 million of SNPs (Takada et al., Genome Res. 2013 Aug;23(8):1329-38. doi: 10.1101/gr.156497.113). We have then analyzed allele specific expression transcriptome-wide using RNA-seq on hybrid F1 cortex generated either in vivo or in vitro from ESCs. In addition, we have used 2 different developmental stages of in vivo cortex (E13.5, P0) and three stages in vitro (undiffererentiated ESC, and differentiated into cortex for 12 and 21 days) to measure the dynamics of parental expression. Please note that [1] the same raw data files were used to generate the ''*allele-specific_sense_read_bases_by_gene_withoutContamination.txt'' processed data files. [2] The samples associated with each file are indicated in the file column header (as their GSM accession numbers). [3] The readme.txt file contains the data processing steps, file description.
In Vitro Corticogenesis from Embryonic Stem Cells Recapitulates the In Vivo Epigenetic Control of Imprinted Gene Expression.
No sample metadata fields
View SamplesASCL1 is known to act as transcriptional activator of notch signaling pathway. We have found that ASCL1 is over expressed in secondary glioblastoma.
System analysis identifies distinct and common functional networks governed by transcription factor ASCL1, in glioma and small cell lung cancer.
Cell line
View SamplesAt mid-log phase (OD600 of 0.5), unique gene expression patterns were observed between these two strains with 3.4% of the transcripts (188/5570) expressed differentially.
A novel oxidized low-density lipoprotein-binding protein from Pseudomonas aeruginosa.
No sample metadata fields
View SamplesTumors have the capacity to trigger the formation of blood vessels allowing them to spread to other body parts. We examined here the stem cells that form arteries and veins within tumors and propose that their inhibition reduces metastatic spread. Overall design: Examination of dynamics and differentiation of tissue resident endothelial hierarchy in a melanoma setting
Endovascular progenitors infiltrate melanomas and differentiate towards a variety of vascular beds promoting tumor metastasis.
Specimen part, Subject
View SamplesRodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology. We generated comprehensive transcriptomes of mouse delta, beta and alpha cells using two separate triple transgenic mouse models generated for this purpose. This enables systematic comparison across thousands of genes between the three major endocrine cell types of the islets of Langerhans whose principal hormones control nutrient homeostasis. Overall design: FACS purified delta or alpha cells and beta cells from the same islets. Islets were isolated from triple transgenic offspring of a cross between mIns1-H2b-mCherry (Jax # 028589) and either Sst-Cre (delta) or Gcg-cre (alpha) cells and a floxed YFP allele to label delta or alpha cells, respectively. Islets from replicate groups of 10 to 12 triple transgenic animals for each group were pooled by sex to obtain sufficient material. Pooled islets were dissociated, sorted and collect in Trizol for RNA isolation and library construction.
Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets.
Sex, Specimen part, Subject
View SamplesGlobal energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis.
Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition.
Specimen part, Time
View SamplesAberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and non-cell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1
Constitutively active Akt induces ectodermal defects and impaired bone morphogenetic protein signaling.
Age, Specimen part
View SamplesP. aeruginosa PAO1 grown as lawns on Nematode Growth Medium prepared without supplementation (NGM Pi<0.1 mM) has high killing ability against C. elegans, however, no mortality in worms has been observed during 48 hrs when feeding on PAO1 lawns grown on phosphate supplemented full NGM Pi 25 mM, pH 6.0 medium.
Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1.
No sample metadata fields
View SamplesDevelopment of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.
Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.
Specimen part
View Samples