Developmental neuronal remodeling is an evolutionarily conserved mechanism required for accurate wiring of mature nervous systems. Despite its fundamental role in neurodevelopment and proposed contribution to various neuropsychiatric disorders, the mechanisms instructing remodeling are only partially known. Here, we uncover the fine temporal transcriptional landscape of a stereotypic remodeling event - that of the Drosophila mushroom body ? neurons. To enrich and complement this developmental expression atlas, we also sequenced developing ? neurons perturbed for three key transcription factors known to regulate pruning. Together, these datasets allowed us to construct the developmental and temporal framework of transcriptional modules that together drive remodeling. Moreover, we identified 10 DNA binding proteins that are involved in various aspects of remodeling, and describe their hierarchical relationships. Overall, this study provides the first broad and detailed molecular insight into the complex regulatory dynamics of developmental neuronal remodeling. Overall design: Transcriptional profiling of drosophila ? neurons during development and when perturbed by EcR-DN, E75 RNAi or Sox14 RNAi. Other adult neurons and astrocyte-like cells also sequenced.
Combining Developmental and Perturbation-Seq Uncovers Transcriptional Modules Orchestrating Neuronal Remodeling.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
View SamplesAnalysis of effect of long-term cryopreservation on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that long-term cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with decreasing signal intensities over time.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
View SamplesAnalysis of cryopreservation effects on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with a strong loss of signal intensities to background levels for several transcripts.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Age, Specimen part
View SamplesAnalysis of long-term freezing on the stability of transcriptome profiles in PAXgene stabilized whole blood samples. In the present study it was tested if long-term freezing of PAXgene RNA tubes (up to one year) has an influence on the transcriptome profile of peripheral whole blood samples. Results indicated that gene expression profiles of whole blood samples stabilized with PAXgene RNA tubes remain stable for at least 1 year.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
View SamplesJoMa1 cells are pluripotent precursor cells, derived from the neural crest of mice transgenic for tamoxifen-inducible c-Myc. Following transfection with a cDNA encoding for MYCN, cells become immortlized even in the absence of tamoxifen.
MYCN and ALKF1174L are sufficient to drive neuroblastoma development from neural crest progenitor cells.
Specimen part, Cell line
View SamplesWe previously demonstrated by genomic and bioinformatical approaches that human macrophage (MF) activation is best described by a spectrum model (Xue et al, Immunity, 2014). MF integrate exogenous input signals on transcriptional level in a unique fashion to generate specific functional programs, enabling the plasticity in disease-related pathophysiologies. Such versatile responsiveness requires fast changes of transcription mediated by transcriptional regulators (TRs) or epigenomic changes. To better understand the principles of this regulation during human MF activation, we assessed histone modifications including H3K4me1, H3K4me3, H3K27me3, and H3K27Ac by ChIP-sequencing allowing us to characterize the functional state of promoters (active, poised, repressed) and enhancers (active, inactive, intermediate). Using transcriptome data from our MF spectrum model, we generated a co-regulation network of all TRs. Next, we overlaid epigenomic information and transcriptional changes of major TRs over time onto the TR network. We observed that input signals like IFN? or TNFa induce a specific network of TRs that are transcriptionally regulated themselves, the combination of regulated TRs changes over time with a boost of transcriptional regulation of dozens of TRs 4 to 12 hrs post input signal exposure, almost all TRs within the network show active promoters, even if the TR itself is not expressed, and similar results are obtained for enhancers with open or at least intermediated states. These findings strongly suggest that in MF, the TR-defined cellular ‘switch panel’ is always accessible thereby allowing MF to quickly respond to the diverse input signal repertoire from the environment. Overall design: Epigenetic analysis of promoter and enhancer sites in primary human macrophage subtypes and correlation to RNA-seq expression data
The transcriptional regulator network of human inflammatory macrophages is defined by open chromatin.
No sample metadata fields
View SamplesA number of key regulators of mouse embryonic stem (ES) cell identity, including the transcription factor Nanog, show strong expression fluctuations at the single cell level. The molecular basis for these fluctuations is unknown. Here we used a genetic complementation strategy to investigate expression changes during transient periods of Nanog downregulation. Employing an integrated approach, that includes high-throughput single cell transcriptional profiling and mathematical modelling, we found that early molecular changes subsequent to Nanog loss are stochastic and reversible. However, analysis also revealed that Nanog loss severely compromises the self-sustaining feedback structure of the ES cell regulatory network. Consequently, these nascent changes soon become consolidated to committed fate decisions in the prolonged absence of Nanog. Consistent with this, we found that exogenous regulation of Nanog-dependent feedback control mechanisms produced more a homogeneous ES cell population. Taken together our results indicate that Nanog-dependent feedback loops play a role in controlling both ES cell fate decisions and population variability.
Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity.
Specimen part
View SamplesThe protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.
MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
Treatment
View SamplesAnalysis of cardiomyocytes cultivated in 2D or age-matched 3D (Engineered heart tissue, EHT) format.
Human Engineered Heart Tissue: Analysis of Contractile Force.
Age, Specimen part
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