Epithelial/mesenchymal transition (EMT) is associated with loss of cell adhesion molecules, such as E-cadherin, and increased invasion, migration, and proliferation in epithelial cancers. In non-small cell lung cancer (NSCLC), EMT is associated with greater resistance to EGFR inhibitors. However, its potential to predict response to other targeted drugs or chemotherapy has not been well characterized. The goal of this study was to develop a robust, platform-independent EMT gene expression signature and to investigate the association of EMT and drug response in NSCLC.
An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance.
Sex, Disease, Treatment, Race
View SamplesTo investigate the role of the circadian clock gene Bmal1 in skeletal muscle, we compared the circadian transcriptomes of fast tibialis anterior (TA) and slow soleus (SOL) skeletal muscles from muscle-specific Bmal1 KO (mKO) and their control Cre- littermates (Ctrl).
Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock.
Sex, Specimen part, Time
View SamplesFetal and adult -globin gene expression is tightly regulated during human development. Fetal globin genes are transcriptionally silenced during embryogenesis through the process of hemoglobin switching. Efforts to understand the transcriptional mechanism(s) behind fetal globin silencing have led to novel strategies to derepress fetal globin expression in the adult, which could alleviate symptoms in hereditary b-globin disorders including sickle cell disease (SCD) and -thalassemia. We identified a novel zinc finger protein, pogo transposable element with zinc finger domain (Pogz), expressed in mouse and human hematopoietic stem and progenitor cells, which represses embryonic b-like globin gene expression in mice. Ablation of Pogz expression in adult hematopoietic cells in vivo results in persistence of embryonic b-like globin expression without significantly affecting erythroid development or mouse survival. Elevated embryonic -like globin expression correlates with reduced expression of Bcl11a, a known repressor of embryonic -like globin expression, in Pogz-/- fetal liver cells. Pogz binds to the Bcl11a promoter, and, to erythroid specific intragenic regulatory regions. Importantly, Pogz+/- mice develop normally, but show elevated embryonic b-like globin expression in peripheral blood cells, demonstrating that reducing Pogz levels results in persistence of embryonic b-like globin expression. Finally, knockdown of POGZ in primary human CD34+ hematopoietic stem and progenitor cell derived erythroblasts, reduces BCL11A expression and increases fetal hemoglobin expression. These findings are significant since new therapeutic targets and strategies are needed to treat the increasing global burden of b-globin disorders.
POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression.
Specimen part
View SamplesA. thaliana plants were grown in 1/2 MS medium in the presence of carbenicillin (10 µg·mL-1) for 1 or 7 days and RNA from their roots extracted and sequenced in Illumina HiSeq 2000/5000 (2x50 bp). Overall design: Total RNA obtained from A. thaliana roots grown in the absence (mock) or presence of carbenicillin (10 µg·mL-1) for 1 or 7 days. Three replicas per experiment.
β-Lactam Antibiotics Modify Root Architecture and Indole Glucosinolate Metabolism in Arabidopsis thaliana.
Specimen part, Subject
View SamplesWe compared the differentially expressed genes between the F9 Wt cells and F9 RAR gamma knock out cells before and after RA treatment. 3 replicates for each conditions.
Gene expression profiling elucidates a specific role for RARgamma in the retinoic acid-induced differentiation of F9 teratocarcinoma stem cells.
No sample metadata fields
View SamplesThe goal of this study was to identify genes that are differentially expressed after genetic deletion of both alleles of the Cyp26a1 gene in murine embryonic stem cells. Cyp26a1 codes for the CYP26A1 enzyme which metabolizes RA to polar RA metabolites, such as 4-oxo-RA and 4-OH-RA. CYP26A1-/- ES cells do not metabolize RA within 48 hours of RA treatment while in Wt ES cells, polar RA metabolites are already detectable by 8 hr. In addition, the absence of CYP26A1 enzyme increases intracellular RA levels. By gene microarray analysis, we wanted to identify genes that would be affected by the lack of the Cyp26a1 gene.
CYP26A1 knockout embryonic stem cells exhibit reduced differentiation and growth arrest in response to retinoic acid.
No sample metadata fields
View SamplesTo gain insight into the molecular changes during OSCC carcinogenesis, we performed unbiased, whole genome deep sequencing (RNA-seq) using RNA isolated from cultured, human TERT-immortalized, non-tumorigenic OKF6-TERT1R and OSCC SCC-9 cells. Overall design: OKF6-TERT1R cells and SCC-9 cells were plated in 10 cm2 tissue culture plates at the density of 2 × 106 cells/plate and treated with 1 µM RA or vehicle (0.1% ethanol) for 48 hours. Experiment includes 3 independent biological replicates.
Altered histone mark deposition and DNA methylation at homeobox genes in human oral squamous cell carcinoma.
No sample metadata fields
View SamplesRetinoic acid receptors (RARs) , and are key regulators of embryonic development. Hematopoietic differentiation is regulated by RAR, and several types of leukemia show aberrant RAR activity. We demonstrate that RAR plays an important role in cellular memory and imprinting by regulating the CpG methylation status of specific promoter regions.
Epigenetic regulation by RARα maintains ligand-independent transcriptional activity.
Cell line, Treatment
View SamplesThe complete transcriptomes of kidney cortex from 3 ?-HIF2aM3 18 month old TG+ male mice and 3 age matched wild type (WT) C57BL/6 male mice were sequenced on an Illumina HiSeq2000 Sequencer. Overall design: Examination of complete transcriptome of kidney cortex between ?-HIF2aM3 TG+ male mice and wild type C57BL/6 male mice
Activation of HIF2α in kidney proximal tubule cells causes abnormal glycogen deposition but not tumorigenesis.
Sex, Specimen part, Cell line, Subject
View SamplesThis study was undertaken in order to characterize the functions of Rex-1 and identify potential Rex-1 target genes.Both alleles of the Rex-1 gene were disrupted in J1 mouse embryonic stem cells. Gene expression levels in one of the resulting Rex-1 knockout cell lines was compared to that of J1 wild type cells.
Analysis of Rex1 (zfp42) function in embryonic stem cell differentiation.
No sample metadata fields
View Samples