Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Conversely, metabolic signals such as redox state, NAD+/NADH and AMP/ADP ratios or heme feed back to and modulate circadian mechanisms to optimize energy utilization across the 24-hour cycle. We show that the signaling molecule carbon monoxide (CO) generated by rhythmic heme degradation is required for normal circadian rhythms as well as circadian metabolic outputs.
Reciprocal regulation of carbon monoxide metabolism and the circadian clock.
Sex, Specimen part
View SamplesFormation 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.
No sample metadata fields
View SamplesGene expression profiling of two different E. coli ABU strains during biofilm growth in human urine.
Global gene expression profiling of asymptomatic bacteriuria Escherichia coli during biofilm growth in human urine.
No sample metadata fields
View SamplesComparison of gene expression profile of E. coli 83972 grown in minimal lab media, in urine and in 3 individual patients.
Global gene expression profiling of the asymptomatic bacteriuria Escherichia coli strain 83972 in the human urinary tract.
No sample metadata fields
View SamplesQuiescent MRC-5 fibroblasts were compared to young fibroblasts Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 6 samples: 3 biological replicates for each age group: young and quiescent MRC-5 cells. 50bp, single-end reads, no strand-specific reads
Long-term quiescent fibroblast cells transit into senescence.
No sample metadata fields
View SamplesRNA-Seq profiling of MCF-7 and MDA-MB-231. We profiled RNA expression in the estrogen-receptor-positive (ER+) MCF-7 and the triple-negative MDA-MB-231 breast cancer cells. The objective was to find genes differentially expressed between these cell lines as potential drivers of invasiveness of the triple-negative MDA-MB-231. We further utilized the identified differential genes to validate expression-responsive module of non-canonical Wnt signaling pathway. Overall design: 2 biological replicates of MCF-7 and 3 biological replicates of MDA-MB-231
Newly Constructed Network Models of Different WNT Signaling Cascades Applied to Breast Cancer Expression Data.
No sample metadata fields
View SamplesTranscriptional profiling of histone methyltransferase SUV39H1-selective small molecule inhibitor F5446-induced genes in human colon carcinoma cells. Tumor cells were treated with F5446 for 48h and used for RNA isolation. The treated cells were compared to untreated control cells. The objective is to identify genes that are regulated by H3K9me3 in the metastatic human colon carcinoma cells.
SUV39H1 regulates human colon carcinoma apoptosis and cell cycle to promote tumor growth.
Treatment
View SamplesRNA-Seq profiling of estrogen-receptor-positive MCF-7 cell lines with different perturbations of non-canonical WNT signaling . The MCF-7 cells were either transfected with an empty vector (pcDNA) or with a ROR2 overexpression construct, in parallel with or without stimulation with recombinant WNT5A. The objective was to find expression-responsive targets of these perturbations as potential drivers of increased cell invasiveness. Overall design: Four conditions of MCF-7 cells each in 3 replicates: 1. empty vector (pcDNA), 2. empty vector (pcDNA) with WNT5A stimulation, 3. ROR2 overexpression construct, 4. ROR2 overexpression construct with WNT5A stimulation
Ror2 Signaling and Its Relevance in Breast Cancer Progression.
No sample metadata fields
View SamplesBone marrow stromal cells (BMSCs) were isolated from the femora and tibiae of irtTA-GBD*-TAg transgenic mice. Using cellular cloning we established skeletal progenitors with distinct differentiation properties and analysed their transcriptome. Unipotent osteogenic and adipogenic cells expressed specific transcriptional programs whereas bipotent clones combined expression of those genes and did not show a unique signature. Overall design: Expression profiling (RNA-seq) of two independent clones from different mice representing skeletal progenitors with the following characteristics: tripotent clones (Osteogenic, Adipogenic, Chondrogenic = OAC1 and OAC2); bipotent clones (Osteogenic, Adipogenic = OA1 and OA2); unipotent clones (Osteogenic = O1 and O2; Adipogenic = A1 and A2). Further, we prepared and sequenced pools of several other clones from these two mice, with the following properties: tripotent clones (Osteogenic, Adipogenic, Chondrogenic = OAC3); bipotent clones (Osteogenic, Adipogenic = OA3; Osteogenic, Chondrogenic = OC3; Adipogenic, Chondrogenic = AC3); unipotent clones (Osteogenic = O3; Adipogenic = A3).
Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors.
Specimen part, Cell line, Subject
View SamplesThe vascular endothelium forms a physical barrier between blood and the surrounding tissue. Its constant exposure to haemodynamic shear stress controls endothelial barrier function which is of major importance for vascular homeostasis. The role of long non-coding RNAs (lncRNAs) in this process remains elusive. Here we identify the shear stress-induced lncRNA LASSIE (linc00520) as a stabilizer of adherens junctions (AJs) in endothelial cells (ECs), that is indispensable for normal endothelial barrier function and shear stress sensing. Silencing of LASSIE in ECs resulted in impaired cell survival, loss of cell-cell contacts and failure to align in the direction of flow. RNA affinity purification followed by mass spectrometry identified several junction proteins associated with LASSIE, including the endothelial adhesion protein PECAM-1 and intermediate filament (IF) protein nestin. Proteomic analysis of VE-cadherin-associated proteins showed that LASSIE silencing reduces VE-cadherin interaction with nestin and microtubule (MT)-associated cytoskeletal proteins. We confirmed that LASSIE silencing results in a decreased connection between VE-Cadherin and the cytoskeleton, resulting in loss of barrier function and shear stress sensing. Together, this study identifies the shear stress-induced lncRNA LASSIE as a critical link between AJs and the IF cytoskeleton, which is indispensable for normal EC junction stabilization and shear stress sensing.
Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function.
Specimen part
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