The goal of this study was to identify YAP/TAZ direct transcriptional targets and transcriptional partners, through ChIP-sequencing and gene expression profiling.
Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth.
Specimen part, Cell lineView Samples
It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown the existence of CD271-expressing neural stem cells (NSCs) in the subventricular zone (SVZ) of Parkinson's disease (PD) patients, which proliferate and differentiate towards neurons and glial cells in vitro. To study the molecular profile of these NSCs in detail, we performed RNA sequencing and mass spectrometry on CD271+ NSCs isolated from human post-mortem SVZ and on homogenates of the SVZ. CD271+ cells were isolated through magnetic cell separation (MACS). We first compared the molecular profile of CD271+ NSCs to the SVZ homogenate from control donors to assess the CD271+ NSCs gene signature and finally made a comparison between controls and PD patients to establish a specific molecular profile of NSCs and the SVZ in PD. While our transcriptome analysis did not identify any differentially expressed genes in the SVZ between control and PD patients, our proteome analysis revealed several proteins that were differentially expressed in PD. Some of these proteins are involved in cytoskeletal organization and mitochondrial function. Transcriptome and proteome analyses of NSCs from PD revealed changes in the expression of genes and proteins involved in metabolism, transcriptional activity and cytoskeletal organization. Our results not only confirm pathological hallmarks of PD (e.g. impaired mitochondrial function), but also suggest that NSCs may transit into a primed-quiescent state, that is in an “alert” non-proliferative phase in PD. Overall design: From post-mortem human SVZ of control and Parkinson disease donors we isolated CD271+ NSCs and Cd11b+ microglia by MACS and the whole SVZ to generate RNA sequencing libraries using Celseq2 method. We aimed for low coverage sequencing (~2 million mapped to the coding regions) per sample to investigate the gross changes in the transcriptome. Libraries (rpi small primer) were sequenced in 3 runs, 2 on an Illumina NextSeq500 using 75-bp paired-end sequencing at the Utrecht Seuqencing center (USEQ) and the third on a HiSeq4000 using 150-bp paired-end sequencing at Genomescan. All the samples were mapped in a single run to an average depth of ~10 million reads per sample. Reads were mapped to the latest human coding transcriptome using bwa, normalized and analyzed using the standard DESEQ2 package.
Transcriptome and proteome profiling of neural stem cells from the human subventricular zone in Parkinson's disease.
Specimen part, SubjectView Samples
The oviducts play a critical role in gamete and embryo transport, as well as supporting fertilization and early embryo development. Progesterone receptor (PGR) is a transcription factor highly expressed in oviductal cells, while its activating ligand, progesterone (P4), surges to peak levels as ovulation approaches. P4 is known to regulate oviduct cilia beating and muscular contractions in vitro, but how PGR may mediate this in vivo is poorly understood. We used PGR-knockout (PRKO) mice to determine how PGR regulates oviductal function during the periovulatory period, in particular oviductal transport and embryo support.
Progesterone receptor-dependent regulation of genes in the oviducts of female mice.
Specimen partView Samples
We aimed to find gene signatures associated with different subgroups of alveolar rhabdomyosarcoma cell lines defined by differences in detection of pro-apoptotic stress
FGFR4 signaling couples to Bim and not Bmf to discriminate subsets of alveolar rhabdomyosarcoma cells.
Specimen part, Cell lineView Samples
Timed sleep restriction designed to mimic human shift work was performed over a 2 week period in mice. On the final day, tissues were collected at 6 hour intervals to exmaine the effects of sleep restriction on circadian gene expression.
Circadian desynchrony promotes metabolic disruption in a mouse model of shiftwork.
Sex, Specimen part, Treatment, TimeView Samples
Aim of this project was the evaluation of the effect of flushing (intraportal and intraoperative) hepatic allografts with tacrolimus before transplantation. Group A was administered tacrolimus, 20ng/ml in 1500ml albumin solution; and Group B was administered only albumin solution. Wedge biopsie of the allograft were harvested after 15 min flushing time and the gene expression profile were determined.
Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial.
Specimen part, TreatmentView Samples
We have correlated transciptomics, proteomics and toponomics analyses of hippocampus tissue of inbred C57/BL6 mice to analyse the interrelationship of expressed genes and proteins at different levels of organization. We find that transcriptome and proteome levels of function are highly conserved between different mice, while the topological organization (the toponome) of protein clusters in synapses of the hippocampus is highly individual, with only few interindividual overlaps (0.15 %). In striking contrast, the overall spatial patterns of individual synaptic states, defined by protein clusters, have boundaries within a strict and non-individual spatial frame of the total synaptic network. The findings are the first to provide insight in the systems biology of gene expression on transcriptome, proteome and toponome levels of function in the same brain subregion. The approach may lay the ground for designing studies of neurodegeneration in mouse models and human brains.
Interlocking transcriptomics, proteomics and toponomics technologies for brain tissue analysis in murine hippocampus.
No sample metadata fieldsView Samples
Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity amongst individuals afflicted with vascular diseases. We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW).
Genetic endothelial systems biology of sickle stroke risk.
Sex, Age, Specimen part, RaceView Samples
This SuperSeries is composed of the SubSeries listed below.
Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation.
Specimen partView Samples