To investigate possible smRNAs linked to TMM silencing by single-stranded and double-stranded silencers, we determined sequences of smRNAs by the Illumina high-throughput sequencing platform and compared silencing efficiency of different strategies. We found that single-stranded silencer alone could promote the production of smRNAs. Overall design: smRNA profiles of 2-week-old wide type seedlings (WT) and different silencers were generated by Illumina Genome Analyzer IIx.
Transcriptional silencing of Arabidopsis endogenes by single-stranded RNAs targeting the promoter region.
Specimen part, Subject
View SamplesMidbrain dopaminergic (mDA) neurons degenerate in Parkinson's disease and are one of the main targets for cell replacement therapies. A comprehensive view of the signals and cell types contributing to mDA neurogenesis is not yet available. By analyzing the transcriptome of the mouse ventral midbrain at tissue and single-cell level during mDA neurogenesis we found that three recently identified radial glia types (Rgl 1-3) contribute to different key aspects of mDA neurogenesis. While Rgl3 expressed most extracellular matrix components and multiple ligands for various pathways controlling mDA neuron development, such as Wnt and Shh, Rgl1-2 expressed most receptors. Moreover, we found that specific transcription factor networks explain the transcriptome expression profiles and suggest a function for each individual radial glia type. Overall design: Triplicate tissue samples from each combination of embryonic day E11.5, E12.5, E13.5, and E14.5 with brain region alar plate, dorsal midbrain, ventral forebrain, ventral hindbrain, and ventral midbrain.
The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.
Specimen part, Subject
View SamplesInvestigations into the roles for Pbx1 and its transcriptional network in dopaminergic neuron development and Parkinson's Disease Overall design: Three samples each from dorsal midbrain, forebrain, hindbrain, Alar plate, and ventral midbrain
The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Specimen part
View SamplesProtein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a bottom-up approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Specimen part
View SamplesProtein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a bottom-up approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Specimen part
View SamplesThe CREB binding protein inhibitor ICG-001 suppresses pancreatic cancer growth
The CREB-binding protein inhibitor ICG-001 suppresses pancreatic cancer growth.
Cell line, Treatment
View SamplesKRAS mutations are present at a high frequency in human cancers. The development of therapies targeting mutated KRAS requires cellular and animal preclinical models. We exploited adeno-associated virus-mediated homologous recombination to insert the KRAS G12D allele in the genome of mouse somatic cells. Heterozygous mutant cells displayed a constitutively active Kras protein, marked morphologic changes, increased proliferation and motility but were not transformed. On the contrary, mouse cells in which we overexpressed the corresponding KRAS cDNA were readily transformed. The levels of Kras activation in knock-in cells were comparable with those present in human cancer cells carrying the corresponding mutation. KRAS-mutated cells were compared with their wild-type counterparts by gene expression profiling, leading to the definition of a "mutated KRAS-KI signature" of 345 genes. This signature was capable of classifying mouse and human cancers according to their KRAS mutational status, with an accuracy similar or better than published Ras signatures. The isogenic cells that we have developed recapitulate the oncogenic activation of Kras occurring in cancer and represent new models for studying Kras-mediated transformation. Our results have implications for the identification of human tumors in which the oncogenic KRAS transcriptional response is activated and suggest new strategies to build mouse models of tumor progression.
Knock-in of oncogenic Kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers.
No sample metadata fields
View SamplesWNT1/beta-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons including the Substantia nigra pars compacta (SNc) subpopulation, whose degeneration is a hallmark of Parkinsons Disease (PD). However, the precise functions of WNT/beta-catenin signaling in this context remain unknown. Using mutant mice, primary ventral midbrain (VM) cells and pluripotent stem cells (mouse embryonic stem cells and induced pluripotent stem cells), we show that Dickkopf 3 (DKK3), a secreted glycoprotein that modulates WNT/beta-catenin signaling, is specifically required for the correct differentiation of a rostrolateral mdDA precursor subset into SNc DA neurons.
Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.
Specimen part
View SamplesThe mechanisms that allow breast cancer cells to metabolically sustain growth are poorly understood. In breast cancer, FoxA1 transcription factor, along with estrogen receptor, regulates luminal cell specification and proliferation. Here we report that FoxA transcription factor family members FoxA1 and FoxA2 fuel cellular growth in breast cancer through the expression of a common target gene, namely the endothelial lipase (LIPG)
FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth.
Cell line
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