The ability of high-risk neuroblastoma to survive unfavorable growth conditions and multimodal therapy is hypothesized to result from a phenomenon known as reversible adaptive plasticity (RAP). RAP is a novel phenomenon enabling neuroblastoma cells to transition between a proliferative anchorage dependent (AD) state and a slow growing anoikis-resistant anchorage independent (AI) state.
A mechanism linking Id2-TGFβ crosstalk to reversible adaptive plasticity in neuroblastoma.
Specimen part
View SamplesSmall molecule curaxin CBL0137 has broad anti-cancer activity in different preclinical models. It interferes with histone-DNA interactions via binding to DNA without causing DNA damage. It resposents first in class "chromatin damaging" agent without genotoxic properties. Its effect on the transcription in human tumor cells was evaluated. DNA-targeting small molecules are widely used for anticancer therapy based on their ability to induce cell death, presumably via DNA damage. DNA in the eukaryotic cell is packed into chromatin, a highly-ordered complex of DNA, histones, and non-histone proteins. These agents perturb chromatin organization. However, the mechanisms, consequences, and impact of the alterations of chromatin structure in relation to their anti-cancer activity is unclear because it is difficult to separate DNA damage and chromatin damage in cells. We recently demonstrated that curaxins, small molecules with broad anticancer activity, bind DNA without causing detectable DNA damage by interfering with histone/DNA interactions and destabilizing the nucleosome. Chromatin unfolding caused by curaxins is sensed by histone chaperone FACT. FACT binds unfolded nucleosomes, which leads to chromatin trapping or c-trapping. In this study, we investigated whether other DNA-targeting small molecules disturb chromatin and cause c-trapping. We found that only compounds directly binding DNA induce chromatin damage and c-trapping. Chromatin damage may occur in the absence of DNA damage and is dependent on the mechanism of compound binding to DNA and its ability to bind chromatinized DNA in cells. We show that FACT is sensitive to a plethora of nucleosomes perturbations induced by DNA-binding small molecules, including displacement of the linker histone, eviction of core histones, and accumulation of negative supercoiling. Most importantly, the cytotoxicity of DNA-binding small molecules correlates with their ability to cause chromatin damage , but not DNA damage. Overall design: HT1080 cells were treated with CBL0137 for 1 hour at 1uM. EU was added for the last 15 minutes. Newly synthesized RNA was isolated using Click-iTâ„¢ Nascent RNA Capture Kit (Invitrogen, cat#C10365) according to manufacturer instruction.
Prevention of Chromatin Destabilization by FACT Is Crucial for Malignant Transformation.
Cell line, Subject
View SamplesUsing microarrays to genotype the parental origin of progeny resulting from a cross between S96 and YJM789 yeast strains, we mapped the distribution of crossovers that occurred during meiosis. Knowledge of the crossover distribution allowed us to assess changes in crossover control in wild type and mutant strains.
Global analysis of the meiotic crossover landscape.
No sample metadata fields
View SamplesInduced pluripotent stem cell (iPSC) technology has the potential to address the inaccessibility of the human brain by providing investigators with patient-specific neurons that can potentially be used to carry out molecular, electrophysiological and pharmacological studies {{855 Takahashi,K. 2006}}. Although iPSC technology was primarily conceived and developed as a means to bypass the use of human embryonic stem cells (hESCs) for regenerative medicine, its potential for disease modeling may prove to be equally valuable, especially for neuropsychiatric disorders.
Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells.
Sex, Age, Specimen part, Time
View SamplesGenes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells.
A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation.
Specimen part
View SamplesSpinal cord injury leads to impaired motor and sensory functions. After spinal cord injury there is a an initial phase of hypo-reflexia followed by a developing hyper-reflexia, often termed spasticity. Previous studies have suggested a relationship between the reappearence of plateau potentials in motor neurons and the development of spasticity after spinalizaion. To understand the moleclar mechanism behind this pheneomona we examined the transcriptional response of the motor neurons after spinal cord injury as it progress over time.
Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.
Sex, Specimen part
View SamplesThe present study was designed to test the hypothesis that limited growth of the fetal liver in the model of maternal fasting is independent of well-characterized signaling mechanisms that are known to regulate somatic growth in adult animals.
Regulation of fetal liver growth in a model of diet restriction in the pregnant rat.
Specimen part, Treatment
View SamplesThe goal of this study was to compare the transcriptional responses of mouse macrophages treated with unsaturated or saturated fatty acids to macrophages treated with LPS to stimulate classical inflammatory activation.
Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells.
Specimen part, Treatment
View SamplesSequencing of 5' ends of RNA molecules from control and exosome-depleted HeLa-S3 cells. Overall design: CAGE library construction from RNA extracted from control and exosome-depleted cells.
Nuclear stability and transcriptional directionality separate functionally distinct RNA species.
No sample metadata fields
View SamplesGene expression programs change during cellular transitions. It is well established that a network of transcription factors and chromatin modifiers regulate RNA levels during embryonic stem cell (ESC) differentiation, but the full impact of post-transcriptional processes remains elusive. While cytoplasmic RNA turnover mechanisms have been implicated in differentiation, the contribution of nuclear RNA decay has not been investigated. Here, we differentiate mouse ESCs, depleted for the ribonucleolytic RNA exosome, into embryoid bodies to determine to which degree RNA abundance in the two states can be attributed to changes in transcription vs. RNA decay by the exosome. As a general observation, we find that exosome depletion mainly leads to the stabilization of RNAs from lowly transcribed loci, including several protein-coding genes. In particular, transcripts that are differentially expressed between states tend to be more exosome sensitive in the state where expression is low. We conclude that the RNA exosome contributes to down-regulation of transcripts with disparate expression, often in conjunction with transcriptional down-regulation. Overall design: CAGE experiments were carried out in mouse embryonic stem cells and embryoid bodies differentiated for three days upon depletion of RRP40 with shRNAs, using a scrambled shRNA as control. The experiments were performed in duplicates
The RNA exosome contributes to gene expression regulation during stem cell differentiation.
Specimen part, Cell line, Subject
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