In this study we investigated changes in gene expression induced by 2cPE (a non-selective isopeptidase inhibitor) in leukemia cells isolated from 10 different patients suffering of B-cell chronic lymphocytic leukemia. We compared 2cPE induced changes in mRNA levels with those induced by bortezomib, another well characterized proteasome inhibitor. Both inhibitors trigger apoptosis in leukemia cells.
The isopeptidase inhibitor 2cPE triggers proteotoxic stress and ATM activation in chronic lymphocytic leukemia cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression.
Specimen part, Treatment
View SamplesRetinoic acid signaling regulates monocyte differentiation into dendritic cells or macrophages. We used microarrays to uncover gene expression changes associated with retinoic acid exposure in human monocytes.
Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression.
Specimen part, Treatment
View SamplesThe microenvironment has profound effect on macrophage phenotype. Here we examine the phenotype of macrophages infiltrating murine undifferentiated pleomorphic sarcomas. We used microarray to examine gene expression profile of tumor-associated macrophages in murine undifferentiated pleomorphic sarcomas.
Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression.
Specimen part
View SamplesWe combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization and “protein-level dependency” studies – a systematic technique that uncovers post-transcriptional regulation – to delineate the network of factors that control the expression of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs vs. embryonic stem cells (ESCs). Through multiparametric data analyses we predict that Tox4 is associating with the Paf1C complex, which maintains cell identity in both cell types and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide a framework for better understanding pluripotency and for dissecting the molecular events that govern the transition from the pre-implantation to the post-implantation state. Overall design: RNA-seq of Tox4 knockdown in mouse EpiSCs
Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells.
No sample metadata fields
View SamplesWe perform RNA sequencing and ribosome profiling time course experiments to examine the effect of fully dysregulating all let-7 targets (in let-7(n2853) animals), partially dysregulating only LIN41 (in lin-41(xe11) animals) or fully dysregulating all let-7 targets while partially dysregulating LIN41 in lin-41(xe11); let-7(n2853) double mutant animals. We conclude that effects on gene expression in let-7 mutant animals are largely and quantitatively explained by dysregulation of LIN41 as its primary target. Furthermore, we identify direct LIN41 target genes regulated on the level of translation or mRNA abundance. Overall design: Total RNA-sequencing time course experiments sampling synchronized worm populations of different genetic backgrounds every two hours over the course of development from late L2/early L3 stage to late L4/Young adult stage.
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Cell line, Subject
View SamplesWe perform RNA sequencing and ribosome profiling time course experiments to examine the effect of fully dysregulating all let-7 targets (in let-7(n2853) animals), partially dysregulating only LIN41 (in lin-41(xe11) animals) or fully dysregulating all let-7 targets while partially dysregulating LIN41 in lin-41(xe11); let-7(n2853) double mutant animals. We conclude that effects on gene expression in let-7 mutant animals are largely and quantitatively explained by dysregulation of LIN41 as its primary target. Furthermore, we identify direct LIN41 target genes regulated on the level of translation or mRNA abundance. Overall design: Ribosome profiling time course experiments sampling synchronized worm populations of different genetic backgrounds every two hours over the course of development from late L2/early L3 stage to late L4/Young adult stage.
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Cell line, Subject
View SamplesRNA-binding proteins (RBPs) are critical regulators of gene expression and elucidating the interactions of RBPs with their RNA targets is necessary to understand how combinations of RBPs control transcriptome expression. The Quaking-related (QR) sub-family of STAR domain RBPs includes developmental regulators and tumor suppressors such as C. elegans GLD-1, which functions as a master regulator of germ line development. To understand how GLD-1 interacts with the transcriptome, we identified GLD-1 associated mRNAs by a ribonomic approach. The scale of GLD-1 mRNA interactions allowed us to determine rules governing GLD-1 target selection and to derive a predictive model where GLD-1 association with mRNA is based on the number and strength of 7-mer GLD-1 binding elements (GBEs) within UTRs. GLD-1/mRNA interactions were quantified, and predictions were verified both in vitro and in live animals, including by transplantation experiments where weak and strong GBEs imposed translational repression of increasing strength on a non-target mRNA.Importantly, this study provides a unique quantitative picture of how an RBP interacts with its mRNA targets. As combinatorial regulation by multiple RBPs is thought to regulate gene expression, quantification of RBP/mRNA interactions should be a way to predict and potentially modify biological outcomes of complex posttranscriptional regulatory networks, and our analysis suggests that such an approach is possible.
A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.
Specimen part
View SamplesThe goal was to identify targets of the RNase REGE-1 by whole RNA sequencing. Overall design: mRNA profiling of C.elegans young adults of rege-1 knockdown or mock RNAi control performed in N2 as well as glp-1 background
Ribonuclease-Mediated Control of Body Fat.
Cell line, Subject
View SamplesEts-4 was previously identified as a suppressor of rege-1(rrr13) phenotype. The goal of this experiment was to identify down-stream regulators of ETS-4, which facilitate this suppression. Overall design: mRNA profiling of C.elegans young adults of ets-4 knockdown or mock RNAi control in the background of rege-1(rrr13)
Ribonuclease-Mediated Control of Body Fat.
Cell line, Subject
View Samples