We examined the transcriptional changes modulated by KDM1A inhibitor NCD-38 by performing global transcriptome analysis. Glioma Stem Cells (GSC10) were treated with either vehicle or NCD-38 for 24 h and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that NCD-38 modulated several genes that are involved in unfolded protein response, endoplasmic reticulum stress pathway and NRF-2 mediated oxidative stress response. Overall design: Total RNA was isolated from the GSC10 cells that were treated with vehicle or NCD-38 for 24 hours. Illumina TruSeq RNA Sample Preparation was performed following manufacturer''s protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.
Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway.
Treatment, Subject
View SamplesAnalysis of gene expression profiles of epididymal fat from DIO rats
Assessment of diet-induced obese rats as an obesity model by comparative functional genomics.
No sample metadata fields
View SamplesMale and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out.
Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.
Specimen part
View SamplesLiver cirrhosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet the mechanisms by which cirrhosis predisposes patients to tumorigenesis are not well understood. Transgenic mice expressing platelet-derived growth factor C (Pdgf-c) under the control of the albumin promoter provide a unique animal model that mimics the step-wise disease progression in humans from fibrosis to HCC. The livers of Pdgf-c Tg mice show evidence of liver injury, including inflammation, proliferation, fibrosis and steatosis, and as the mice age, angiogenesis and dysplasia. Eighty-five percent of these mice develop HCC spontaneously, and have reduced survival that is related to their liver pathology. Through measurement of protein, RNA, and histological markers, we provide evidence to support the hypothesis that changes in liver stromal cells play an essential role in tumorigenesis in this model. A paracrine signaling model is proposed where ectopic expression of Pdgf-c in hepatocytes results in activation of hepatic stellate cells, which subsequently activates endothelial and Kupffer cells. Activation of these non-parenchymal cells promotes the release of hepatocyte growth factors that, together with changes in extracellular matrix, lead to the formation of HCC. Pdgf-c Tg mice provide a useful pre-clinical model in which to test novel drugs for chronic liver disease and HCC that focus on blocking the processes that alter the liver's fibrotic microenvironment.
Paracrine activation of hepatic stellate cells in platelet-derived growth factor C transgenic mice: evidence for stromal induction of hepatocellular carcinoma.
Specimen part
View SamplesHeme-regulated eIF2 kinase (HRI) is essential for the survival of erythroid precursors in iron and heme deficiency and it also plays a protective role in red blood cell diseases of erythroid protoporphyria and -thalassemia. In this study, we demonstrated for the first time the impairment of GATA-1 and Fog-1 expressions in iron deficiency and the impairment of GATA-1 expression in -thalassemia. Furthermore, HRI is necessary to maintain the GATA-1/Fog-1 induced functions in erythroid differentiation, cell cycle and cell survival by sustaining both expressions of GATA-1 and Fog-1 in iron deficiency and in -thalassemia.
Haem-regulated eIF2alpha kinase is necessary for adaptive gene expression in erythroid precursors under the stress of iron deficiency.
Specimen part
View Samples5 arrays from obese insulin-resistant and lean insulin-sensitive females adipose tissue at fasting and after 3h hyperinsulinemia
Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects.
Sex, Specimen part
View SamplesUnderstanding the biological potential of fetal stem/progenitor cells will help define mechanisms in liver development and homeostasis. We isolated epithelial fetal human liver cells and established phenotype-specific changes in gene expression during continuous culture conditions. Fetal human liver epithelial cells displayed stem cell properties with multilineage gene expression, extensive proliferation and generation of mesenchymal lineage cells, although the initial epithelial phenotype was rapidly supplanted by meso-endodermal phenotype in culture. This meso-endodermal phenotype was genetically regulated through cytokine signaling, including transforming growth factor-b, bone morphogenetic protein, fibroblast growth factors, and other signaling pathways. Reactivation of HNF-3a (FOXA1) transcription factor, a driver of hepatic specification in the primitive endoderm, indicated that the meso-endodermal phenotype represented an earlier developmental stage of cells. We found that fetal liver epithelial cells formed mature hepatocytes in vivo, including after genetic manipulation using lentiviral vectors, offering convenient assays for analysis of further cell differentiation and fate. Taken together, these studies demonstrated plasticity in fetal liver epithelial stem/progenitor cells, offered paradigms for defining mechanisms regulating lineage switching in stem/progenitor cells, and provided potential avenues for regulating cell phenotypes for applications of stem/progenitor cells, such as for cell therapy.
Phenotype reversion in fetal human liver epithelial cells identifies the role of an intermediate meso-endodermal stage before hepatic maturation.
Specimen part
View SamplesWe performed single-cell RNA sequencing (RNA-seq) during the in vitro transition of mouse ESCs (mESCs) from a naïve pluripotent state into epiblast-like cells (EpiLCs), a primed pluripotent state. We derived pseudotime expression trajectories to investigate transcript dynamics of key metabolic regulators, with the aim to identify metabolic pathways that potentially impact on early embryonic cell state transitions. Overall design: Single-cell RNA-seq during the in vitro differentiation of mouse embryonic stem cells (ESCs) in 2i culture conditions (time point t=0h) into epiblast-like cells (EpiLCs) at time points t=24h and t=48h.
Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate.
Specimen part, Cell line, Subject
View Sampleswe report single cell expression profiles of embryonic cells (from day 5 to 11) of pig embryo development. Overall design: single cell transcriptomes were generated from 220 cells obtained from 28 embryos (15 male and 13 female)
Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis.
Specimen part, Subject
View SamplesPurpose: Utilized Next-generation sequencing (NGS) to profile transcriptional differences between two populations, carriers (CC) of rs10846744 SNP associated with cardiovascular disease (CVD) and non-carriers (GG) who are disease free. Methods: Total RNA was isolated from three subjects homozygous for the rs10846744 reference (GG) allele and three subjects homozygous for the rs10846744 risk (CC) allele and then subjected to full transcriptome sequencing using the Perkin Elmer next gen sequencing platform (Perkin Elmer, Branford, CT). Bioinformatics was performed using Perkin Elmer GeneSifter software program. The data was adjusted by selecting total map reads, quality reads >20, log transformation, and using Benjamini Hochberg to correct for multiple testing. RNA targets of interest were validated by qRT–PCR using TaqMan assays and western blotting using standard methodologies. Results: Using Perkin Elmer''s Genesifter Analysis Edition Software, we mapped about 100 million sequence reads per sample to the human genome (build 37.2), normalized the raw read count by total mapped million reads and identified 937 upregulated and 587 downregulated transcripts in the EBV (Epstein Barr Virus)-transformed B lymphocyte cells isolated from 3 carriers of the risk (CC) allele and 3 non-carriers of the (GG) reference allele with BWA workflow. RNA-seq data confirmed differential expression of LAG3 and this was validated with qRT–PCR. Conclusions: Our study represents the first detailed analysis of differential LAG3 expression, contributing to CVD, with biologic replicates, generated by RNA-seq technology. Overall design: mRNA transcriptional profiles from EBV (Epstein Barr Virus)-transformed B lymphocyte cells, isolated from 3 carriers of the risk (CC) allele and 3 non-carriers of the (GG) reference allele, were generated by deep sequencing, in triplicate, using Illumina platform technology.
Lymphocyte activation gene 3 and coronary artery disease.
Specimen part, Subject
View Samples