Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA152241 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Combinatorial control of gene expression is presumed to be mediated by molecular interactions between coincident transcription factors (TFs). While information on the genome-wide locations of TFs is available, the genes they regulate and whether they function combinatorially often remain open questions. Here, we developed a mechanistic, rather than statistical, modeling approach to elucidate TF control logic from gene expression data. Applying this approach to hundreds of genes in 85 datasets measuring the transcriptional responses of murine fibroblasts and macrophages to cytokines and pathogens, we found that stimulus-responsive TFs generally function sequentially in logical OR gates or singly. Logical AND gates were found between NFB-responsive mRNA synthesis and MAPKp38-responsive control of mRNA half-life, but not between temporally coincident TFs. Our analyses identified the functional target genes of each of the pathogen-responsive TFs and prompts a revision of the conceptual underpinnings of combinatorial control of gene expression to include sequentially acting molecular mechanisms that govern mRNA synthesis and decay.
2017-02-01 | GSE35521 | GEO
Project description:An iterative Systems Biology approach reveals how the pathogen-responsive transcriptome is specified by combinatorial codes of nuclear transcription factors, cytoplasmic mRNA halflife regulators, and autocrine mechanisms.
2016-04-24 | GSE68318 | GEO
Project description:In response to stress, cells activate signaling pathways that coordinate broad changes in gene expression to enhance cell survival. Remarkably, complex variations in gene expression occur even in isogenic populations and in response to similar signaling inputs. However, the molecular mechanisms underlying this variability and their influence on adaptive cell fate decisions are not fully understood. Here, we use scRNA-seq to longitudinally assess transcriptional dynamics during osmoadaptation in yeast. Our findings reveal highly heterogeneous expression of the osmoresponsive program, which organizes into combinatorial patterns that generate distinct cellular programs. The induction of these programs is favored by global transcriptome repression upon stress. Cells displaying basal expression of the osmoresponsive program are hyper-responsive and resistant to stress. Through a transcription-focused analysis of more than 300 RNA-barcoded deletion mutants, we identify genetic factors that shape the heterogeneity of the osmostress-induced transcriptome, define regulators of stress-related subpopulations and find a link between transcriptional heterogeneity and increased cell fitness. Our findings provide a regulatory map of the complex transcriptional phenotypes underlying osmoadaptation in yeast and highlight the importance of transcriptional heterogeneity in generating distinct adaptive strategies.
2025-02-04 | GSE274661 | GEO
Project description:Pathogen infection triggers transcriptional reprogramming in host plants, however we still know little about the dynamics of the pathogen-induced defense transcriptome. The goal of this study was to investigate the dynamic reprogramming of the defense transcriptome in response to Fusarium oxysporum infection in Arabidopsis using RNA-seq technology and to provide a comprehensive analysis of genes underlying the innate immune response against the fungal pathogen. Our results suggest that the Arabidopsis transcriptome is reprogrammed to co-ordinately express multiple positive and negative regulators following pathogen infection to modulate defense gene expression and disease resistance. Our study identified a number of novel genes responsive to pathogen infection and provided a rich source of pathogen responsive genes for further functional characterization. Four samples (M1DPI, M6DPI, F1DPI and F6DPI; M=mock treated; F=Fusarium oxysporum infected; DPI=day post inoculation) were sequenced to identify pathogen responsive genes in each time point. Each sample was sequenced once, i.e. without biological replicate.
2012-06-01 | E-GEOD-34241 | biostudies-arrayexpress
Project description:Combinatorial Control Logic of the Gene Expression Response to Endotoxin links Signal-Dependent Transcriptional Factors and Cytoplasmic Mechanisms
| PRJNA282421 | ENA
Project description:Metabolic reprogramming is an important feature of host-pathogen interactions and a hallmark of tumorigenesis. The intracellular apicomplexa parasite Theileria induces a Warburg-like effect in host leukocytes by hijacking signaling machineries, epigenetic regulators and transcriptional programs to create a transformed cell state. The molecular mechanisms underlying host cell transformation are unknown. Here we show that a parasite-encoded prolyl-isomerase, TaPin1, stabilizes host pyruvate kinase isoform M2 (PKM2) leading to HIF-1α-dependent regulation of metabolic enzymes, glucose uptake and transformed phenotypes in parasite-infected cells. Our results provide a direct molecular link between the secreted parasite TaPin1 protein and host gene expression programs. This study demonstrates the importance of prolyl isomerization in the parasite manipulation of host metabolism.
2019-11-13 | PXD012895 | Pride
Project description:Pathogen infection triggers transcriptional reprogramming in host plants, however we still know little about the dynamics of the pathogen-induced defense transcriptome. The goal of this study was to investigate the dynamic reprogramming of the defense transcriptome in response to Fusarium oxysporum infection in Arabidopsis using RNA-seq technology and to provide a comprehensive analysis of genes underlying the innate immune response against the fungal pathogen. Our results suggest that the Arabidopsis transcriptome is reprogrammed to co-ordinately express multiple positive and negative regulators following pathogen infection to modulate defense gene expression and disease resistance. Our study identified a number of novel genes responsive to pathogen infection and provided a rich source of pathogen responsive genes for further functional characterization.
2012-06-01 | GSE34241 | GEO
Project description:Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most severe congenital heart defect encompassing a spectrum of left-ventricular hypoplasia occurring in association with outflow-tract obstruction. The current clinical paradigm assumes HLHS is largely of hemodynamic origin. Here, by combining whole-exome sequencing of 87 HLHS parent-offspring trios and transcriptome of cardiomycytes (CMs) from healthy and patient native ventricles at different stages of development we identified perturbations in coherent gene programs controlling ventricular muscle lineage development. Single-cell and 3D molecular/functional modeling with iPSCs demonstrated intrinsic defects in the cell-cycle/ciliogenesis/autophagy hub resulting in disrupted differentiation of early cardiac progenitor (CP) lineages and ultimate defective CM-subtype differentiation/maturation in HLHS. Moreover, premature cellcycle exit of ventricular CM prevents tissue response to cues of developmental growth leading to multinucleation/polyploidy, accumulation of DNA damage, exacerbated apoptosis, and eventually ventricle hypoplasia. Our results highlight how genetic heterogeneity in HLHS converges in perturbations of sequential cellular processes driving cardiogenesis and facilitate potential novel nodes for therapy beside surgical intervention.
2022-02-15 | PXD014812 | Pride
Project description:Extracellular matrix (ECM) is the first line of defense which is an inimitable organelle that perceives biotic and abiotic stresses and reprograms biological processes of host. It also activates innate immune responses in temporal and spatial manner and acts as physical scaffold that prevents the entry of pathogen and microbes in response to stress and hormonal signals. Stem rot, caused by Macrophomina phaseolina adversely affects fiber production in jute. However, how wall related susceptibility affects ECM proteome remains undetermined in bast fiber crops. Here, stem rot responsive quantitative temporal ECM proteome was developed in jute upon M. phaseolina infection. Using isobaric tags for relative and absolute quantitative proteomics and MS/MS analysis, we identified 415 disease responsive proteins (DRPs), involved in wall integrity, acidification, proteostasis, hydration and redox homeostasis. Disease-related correlation network identified functional hubs related to wall degrading enzymes, structural carbohydrates and signaling govern rot responsive wall-susceptibility.
2024-05-21 | PXD046937 | Pride
Project description:The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene modules in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Module network analysis linked established regulators like Neurog3 to unrecognized roles in endocrine secretion and protein transport, and nominated multiple candidate regulators of pancreas development. Phenotyping mutant mice revealed that candidate regulatory genes encoding transcription factors, including Bcl11a, Etv1, Prdm16 and Runx1t1, are essential for pancreas development or glucose control. Our integrated approach provides a unique framework for identifying regulatory networks underlying pancreas development and diseases like diabetes mellitus. Gene expression analysis: 12 primary cell populations from wild-type pancreas and 1 cell type from a mutant background (E15 Ngn3-null cells) pancreas (in fetal and adult stage) were purified using a combination of cell surface markers and transgenic reporters. Total RNA was isolated from each cell type in at least biological triplicates, amplified and hybridized to Affymetrix Mouse 430 2.0 arrays.
2014-10-16 | E-GEOD-54374 | biostudies-arrayexpress