This SuperSeries is composed of the SubSeries listed below.
Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes.
Specimen part, Disease
View SamplesThe mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis.
Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes.
Specimen part, Disease
View SamplesColon cancer cell lines with partial sensitivity to the BRAF inhibitor PLX4720 were grown in increasing concentration of the drug to develop acquired resistance. Gene expression was performed for comparison of the resistant clones to the parental lines.
Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents.
Specimen part, Cell line
View SamplesIn this study, we used the Affymetrix HG-U133A 2.0 GeneChip for deriving a multigenic classifier capable of predicting HCV+cirrhosis with vs without concomitant HCC.
Identifying genes for establishing a multigenic test for hepatocellular carcinoma surveillance in hepatitis C virus-positive cirrhotic patients.
Specimen part, Disease, Disease stage
View SamplesStudies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GSIS) and change the expression of genes in pancreatic β-cells. Still the mechanisms linking vitamin D and GSIS are unknown.
Vitamin D metabolites influence expression of genes concerning cellular viability and function in insulin producing β-cells (INS1E).
Specimen part, Cell line, Treatment
View SamplesDuring hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into distinct cell fates are not fully understood. Here, we identify chromatin-regulating and cell-fate-determining transcription factors (TF) governing dendritic cell (DC) development by annotating the enhancer and promoter landscapes of the DC lineage. Combining these analyses with detailed over-expression, knockdown and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, differential activity of TF can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes. Overall design: Here analyzed 2 experiments, each one contains samples of moDC and pDC ex vivo cultured cells. The first experiment contains 32 samples of moDC and pDC following stimulation with various TLR stimulators. The second experiment contains 8 samples of moDC and pDC following perturbations; Cebpb and Irf8 knock down or over expression.
A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin States.
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View SamplesThe gene regulatory network in naïve mouse embryonic stem cells (ESCs) must be reconfigured for lineage competence. Tcf3 enables rewiring to formative pluripotency by repressing components of the ESC transcription factor circuitry. However, elimination of Tcf3 only delays, and does not prevent, state transition. Here we delineate distinct contributions of the Ets-family transcription factor Etv5 and the repressor Rbpj. Downstream of Erk1/2 signalling, Etv5 activates enhancers for formative pluripotency. Concomitant up-regulation of Rbpj ensures irreversible exit from the naïve state by extinguishing reversal factors, Nanog and Tbx3. Triple deletion of Etv5, Rbpj and Tcf3 incapacitates ESCs, such that they remain undifferentiated and locked in self-renewal even in the presence of differentiation stimuli. Thus, pluripotency progression is driven hierarchically by two repressors, that respectively dissolve and extinguish the naive network, and an initiator that commissions the formative network. Similar tripartite action may be a general mechanism for efficient cell transitions. Overall design: RNA-seq analysis of parental Rex1-GFPd2 ES cells (RGd2), and deletion mutants generated in this background (Etv5-KO, RbpJ-KO, Etv5-RpbJ-dKO, Etv5-RbpJ-Tcf3-tKO) cultured in 2i, N2B27 or supplemented with Chiron, 3 biological replicates per condition.
Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.
Subject
View SamplesT4 and T5 neurons are components of the neuronal circuit for motion vision in flies. To identify genes involved in neuronal computation of T4 and T5 neurons, we perfomed transcriptome analysis. Nuclei of T4 and T5 neurons were immunoprecipitated, total RNA was harvested and used for mRNA-seq with Illumina technology. In two biological replicates, we mapped 154 and 119 million reads to D. melanogaster genome. mRNA-seq provided information about expression levels of 17,468 annotated transcripts in the T4 and T5 neurons. Overall design: Cell type – specific transcriptome analysis of the RNA isolated from immunoprecipitated nuclei, performed in two biological replicates
RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.
Subject
View SamplesTranscriptional microarray analysis was conducted on gastrocnemius muscle of control and PGC-1(i)skm-/- mice one week after the last tamoxifen administration using the Affymetrix Mouse Gene 1.0 ST.
The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles.
Specimen part
View SamplesThe activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear.
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
Specimen part
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