Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube. Upon loss of neuronal flt1, ectopic sprouts emanate from veins involving special angiogenic cell behaviors including nuclear positioning and a molecular signature distinct from primary artery or secondary venous sprouting. Manipulation of AV identity or Notch signaling established that ectopic sprouting in flt1 mutants requires venous endothelium. Conceptually our data suggest that spinal cord vascularization proceeds from veins involving two-tiered regulation of neuronal sFlt1 and Vegfaa via a novel sprouting mode. Overall design: Examination of wildtype (3 biological replicates, with two technical replicates each) and flt1ka601 homozygous mutants (3 biological replicates, with two technical replicates each)
Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization.
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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 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 SamplesThe miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells.
The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
Specimen part
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 SamplesNeuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK.
Targeted expression of mutated ALK induces neuroblastoma in transgenic mice.
Specimen part
View SamplesHere we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases. Overall design: Examination of GMPs in six different conditions by RNA-seq
Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
Specimen part, Subject
View Samples