This SuperSeries is composed of the SubSeries listed below.
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Cell line, Treatment
View SamplesThe indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favored development of epigenetic drugs. In this study, we have design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of hematological neoplasia (Acute Myeloid Leukemia-AML, Acute Lymphoblastic Leukemia-ALL and Diffuse Large B-cell Lymphoma-DLBCL) with the lead compound CM-272, inhibited cell proliferation and promoted apoptosis, inducing interferon stimulated genes and immunogenic cell death. CM-272 significantly prolonged survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series, as a promising therapeutic tool for unmet needs in hematological tumors.
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Cell line, Treatment
View SamplesBovine papillomavirus (BPV) is the causative agent of papillomatosis in cattle. The disease causes cutaneous and mucosal lesions that can be minimized or lead to the appearance of malignant tumors. This study aims to identify possible molecular mechanisms that are behind the pathological processes associated with bovine papillomatosis through the identification of genes related to the development of the lesions. For this, next-generation RNA sequencing was used to assess differentially expressed genes in infected by BPV and non-infected bovines. Three animals with papillomatosis lesion and three without papillomatosis lesion were studied. The Galaxy platform was used to analyze the data generated by the sequencing. The Illumina output files were converted to FASTQ format. Quality evaluation was performed using FastQC and the sequence quality cut was performed using Trimmomatic. TopHat and Bowtie were used to map and align the reads with the reference genome. The abundance of the expressed genes was verified using Cuffilinks. Cuffdiff was used for differential expression analysis. Functional annotation of the differentially expressed genes was performed using Gene Ontology (GO) databases. RNA-sequencing generated a total of 121,722,238 of reads. In the gene expression analysis, a total of 13,421 genes expressed were identified and of these 1343 were differentially expressed. The functional annotation of differentially significant genes showed that many genes presented functions or they were related to metabolic pathways associated with the progression of papillomatosis lesions and cancer development in cattle. Although more studies are needed, this is the first study that focused on a large-scale evaluation of gene expression associated with the BPV infection, which is important to identify possible mechanisms regulated by the host genes that are necessary the development of the lesion Overall design: Analysis of three BPV infected and three BPV non-infected samples
Comparative transcriptomic analysis of bovine papillomatosis.
Age, Specimen part, Treatment, Subject
View SamplesThe global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed -cell dysfunction in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet was observed to alter gene expression of pancreatic islet genes in adult female offspring (P < 0.001); affected functional clusters includes calcium ion binding, insulin, apoptosis, Wnt and cell cycle organ/system development. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.
Sex
View SamplesReactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation.
Genomic analysis of reactive astrogliosis.
Sex, Specimen part, Treatment
View SamplesThe development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Sex, Specimen part
View SamplesProfiling of gene expression in Vastus Lateralis from female patients before and after GBP surgery and from lean Control
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Sex, Specimen part
View SamplesWe report the generation of induced oligodendrocyte precursor cells (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to convert mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures that resemble OPCs.
Generation of oligodendroglial cells by direct lineage conversion.
Specimen part
View SamplesSpleen and lymph node dendritic cells have a differential capacity do induce and retain iTreg cells. Therefore we performed a comparative analysis of the dendritic cells derived from these two compartments to identify the responsible genes
Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells.
Specimen part
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