Basic helix-loop-helix (bHLH) proneural transcription factors (TFs) Ascl1 and Neurog2 are integral to the development of the nervous system. Here, we investigated the molecular mechanisms by which Ascl1 and Neurog2 control the acquisition of generic neuronal fate and impose neuronal subtype identity. Using direct neuronal programming of embryonic stem cells, we found that Ascl1 and Neurog2 regulate distinct targets by binding to largely different sets of sites. Their divergent binding pattern is not determined by the previous chromatin state but distinguished by specific E-box enrichments which reflect the DNA sequence preference of the bHLH domain. The divergent Ascl1 and Neurog2 binding patterns result in distinct chromatin accessibility and enhancer activity landscapes that shape the binding and activity of downstream TFs during neuronal specification. Our findings suggest that proneural factors contribute to neuronal diversity by differentially altering the chromatin landscapes that shape the binding of neuronally expressed TFs. Overall design: Single-cell RNA-seq was used to characterize gene expression in mixed populations of mES cells containing induced expression of either Ascl1 or Neurog2.
Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes.
Specimen part, Treatment, Subject
View SamplesTo explore events that govern the differentiation of human nave B cells (NBCs) into memory B cells and plasma cells (PCs), we designed an in vitro 2-step culture model leading non-switched NBC precursors to differentiate into two cell compartments: CD20loCD38hi and CD20+CD38+.
IL-2 requirement for human plasma cell generation: coupling differentiation and proliferation by enhancing MAPK-ERK signaling.
Specimen part, Subject, Time
View SamplesHuman bone marrow mesenchymal stromal cells (BM-MSC) could be committed toward a functional lymphoid-like stroma by a combination of TNFalpha (TNF) and Lymphotoxin alpha1/beta2 (LT) (Am-Thomas et al Blood 2007).
Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes.
Sex, Specimen part, Treatment
View SamplesGene expression profiling based classification of DLBCL patients versus healthy donors provides insights on transcriptional regulation processes.
T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells.
Sex, Age, Specimen part
View SamplesExpression profiles at various time points after surgical intervention for pressure-overload induced cardiac hypertrophy and failure.
Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective protein.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesThe basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. However, nucleosome number in cells was considered fixed, and no condition was described where nucleosome number was reduced. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker and variant histones, and a correspondingly reduced number of nucleosomes. Yeast nhp6 mutants lacking NHP6A and B proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform, and our results can be modelled assuming that different nucleosomal sites compete for the available histones: sites with high affinity are almost always packaged into nucleosomes both in wt and nucleosome-depleted cells, whereas sites with low affinity are less frequently packaged in nucleosome-depleted cells. We suggest that by modulating the occupancy of nucleosomes histone availability may constitute a novel layer of epigenetic regulation.
Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output.
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View SamplesTh17 cells were sorted ex vivo from PB of healthy donors as CD4+CD161+CCR6+CXCR3-. Following, cells were transduced with a lentiviral vector carrying the Eomes gene or with an empty vector. Infected cells were then enriched by MACS separation using the reporter gene NGFR as selection marker. Finally, cells were frozen for RNA analysis.
Eomes controls the development of Th17-derived (non-classic) Th1 cells during chronic inflammation.
Cell line
View SamplesWe exploited microarrays to detail the global program of gene expression underlying normal stem cells and cancer stem cells in the cerebellum and in medulloblastomas (MBs).
Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification.
Specimen part
View SamplesGene expression study of DSG2 silenced human microvascular endothelial cells
Desmoglein-2-integrin Beta-8 interaction regulates actin assembly in endothelial cells: deregulation in systemic sclerosis.
Specimen part
View SamplesIn this study we applied differential gene expression analysis to exfoliated human urothelia obtained from patients of known bladder disease status. Selected targets from the microarray data were validated in an independent set of samples using a quantitative PCR approach.
A candidate molecular biomarker panel for the detection of bladder cancer.
Specimen part, Disease
View Samples