Analysis of gene-probe expression data (FPKM) for mouse skin using single-end read RNA-seq Overall design: RNA was collected and analyzed for 2 biological replicates each from 3 developmental stages (E18.5, P3, 10 weeks)
RNA-seq studies reveal new insights into p63 and the transcriptomic landscape of the mouse skin.
No sample metadata fields
View SamplesWe developed a Tet-inducible system to express deltaNp63alpha isoform under the control of keratin 5 promoter. Transgenic mice, which were Bigenic (BG) developed a severe skin phenotype with abnormal keratinocyte differentiation and defects in hair follicle development and cycling. Skin samples from transgenic animals and wild type animals were analyzed for global transcriptome changes.
Abnormal hair follicle development and altered cell fate of follicular keratinocytes in transgenic mice expressing DeltaNp63alpha.
Specimen part
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MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Treatment
View SamplesSpecific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Treatment
View SamplesAnalysis of gene expression changes during mouse salivary gland development using RNA-Seq Overall design: RNA was collected and analyzed for at least two biological replicates each from six developmental timepoints (E14.5, E16.5, E18.5, P5, 4 weeks, 12 weeks)
RNA-seq based transcriptomic map reveals new insights into mouse salivary gland development and maturation.
Age, Specimen part, Cell line, Subject
View SamplesOxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin.
Systems genetics analysis of gene-by-environment interactions in human cells.
Sex, Subject
View SamplesAnalysis of gene-probe expression data (FPKM) for HNSCC cell-lines using single-end RNA-Seq Overall design: RNA was collected and analyzed from 6 HNSCC cell-lines ( SCC15, SCC4, SCC71, UMSCC103, UMSCC29, SCC351)
A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues.
No sample metadata fields
View SamplesDiminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms leading to ageing remain elusive. We present a proteome-wide atlas of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) along with five other cell types that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified was assessed in a cohort of healthy human subjects from different age. As the HPCs became older, pathways in central carbon metabolism exhibited features reminiscent of the Warburg effect where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation revealed a reduced functionality and a bias towards myeloid differentiation at the expense of lymphoid development. Ageing caused significant alterations in the bone marrow niche too, such as functionality of the pathways involved in HPC homing and lineage differentiation. The data represents a valuable resource for further in-depth mechanistic analyses, and for validation of knowledge gained from animal models. Overall design: RNA-seq samples extracted from human bone marrow, from 6 cell populations (HPC, LYM, MON, ERP, GRA, MSC). Technical replicates are included for each donor and cell type. Technical replicates were produced by making independent libraries from the same RNA.
Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells.
Sex, Age, Specimen part, Subject
View SamplesWe conducted a set of lab-evolution experiments in yeast and followed the long-term dynamics of aneuploidy under diverse conditions including heat shock and high PH.
Chromosomal duplication is a transient evolutionary solution to stress.
No sample metadata fields
View SamplesCancer cells have abnormal gene expression profiles, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila epithelial tissues and combined in vivo genetics with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that the bulk of the tumor specific gene expression is driven by an ectopic network of a few transcription factors that are overexpressed and/or hyperactivated in tumor cells. These factors are Stat, AP-1, the bHLH proteins Myc and AP-4, the nuclear hormone receptor Ftz-f1, the nuclear receptor coactivator Taiman/AIB1, and Mef2. Notably, many of these transcription factors are also hyperactivated in human tumors. Bioinformatics analysis predicted that these factors directly regulate the majority of the tumor specific gene expression, that they are interconnected by extensive cross-regulation, and that they show a high degree of co-regulation of target genes. Indeed, the factors of this network were required in multiple epithelia for tumor growth and invasiveness and knock-down of individual factors caused a reversion of the tumor specific expression profile, but had no observable effect on normal tissues. We further found that the Hippo pathway effector Yki/Sd was strongly activated in tumor cells and initiated cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control tumor cell specific gene expression. Overall design: RNA-seq gene expression profiling across Drosophila 3rd instar larval wild type wing discs and genetic perturbations of wts.
An Ectopic Network of Transcription Factors Regulated by Hippo Signaling Drives Growth and Invasion of a Malignant Tumor Model.
Subject, Time
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