Purpose: Citron kinase (CitK) knockout mice show a severe form of primary microcephaly, associated with ataxia and lethal epilepsy. This phenotype is caused by massive apoptosis occuring during embryonic and post-natal brain development, associated with cytokinesis failure. Cerebellum is the tissue showing highest sensitivity to CitK loss. The clinical phenotype of CitK knockout mice is significantly resued by P53 inactivation. In addition, CitK/P53 double knockout brains have almost normal levels of apoptosis, but display high percentage of binucleated and multinucleated cells. The aim of this study was to analyze the gene expression changes produced in developing neural tissue by CitK loss and to determine which alterations are P53-dependent. expression changes Methods: We analyzed by RNA sequencing total RNA extracted from P4 cerebellum of mice characterized by the following genotypes: 1. CitK +/-, P53 +/- (CTRL); 2. CitK -/-, P53 +/- (CitK-KO); 3. CitK +/-, P53 -/- (P53-KO); 4. CitK -/-, P53 -/- (D-KO). Biological triplicates were analyzed per every genotype. Conclusions: The loss of CitK leads to a strong reduction of the expression of pro-neural genes and induces a P53-related pro-apoptotic gene sets. The analysis of D-KO mice reveals that most of these changes are P53-dependent, but many genes implicated in growth arrest are induced through P53-independent mechanisms. Overall design: Cerebellar mRNA profiles of 4-day old mice of CTRL, CitK-KO, P53-KO and D-KO mice were generated by deep sequencing, in triplicate, using Illumina HiScan SQ
ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly.
Specimen part, Cell line, Subject
View SamplesN-octanoyl dopamine (NOD), but not dopamine dose dependently induces the UPR. This was also found for other synthetic N-Acyl dopamine derivates (NADD). Induction of the UPR was dependent on the redox activity of NADD and was not caused by selective activation of a particular UPR sensor. UPR induction did not result in cell apoptosis, yet NOD strongly impaired cell proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK. These cells were significantly more resistant to cold inflicted injury.
N-octanoyl dopamine treatment of endothelial cells induces the unfolded protein response and results in hypometabolism and tolerance to hypothermia.
Cell line, Treatment
View SamplesStudy the effects of serum starvation for 24hrs on 4 cell types - TERV, TERV-ST, TERV-ST110, TERV-ASB56.
Signaling and transcriptional changes critical for transformation of human cells by simian virus 40 small tumor antigen or protein phosphatase 2A B56gamma knockdown.
Cell line
View SamplesThe chemokine decoy receptor D6 internalises and degrades inflammatory CC chemokines enabling resolution of inflammation. In D6 deficient mice (D6 KO), otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study we have used transcriptomic approaches to define the molecular make up of this response.
Microarray analyses demonstrate the involvement of type I interferons in psoriasiform pathology development in D6-deficient mice.
Sex, Specimen part, Treatment, Time
View SamplesBackground: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder.
Identification of the BRD1 interaction network and its impact on mental disorder risk.
Cell line
View SamplesPrevious in vitro studies in our lab have shown that CD24, a cell surface receptor, actively regulates lipid accumulation in adipocytes. But how CD24 regulates this process remains unknown. In order to answer this question, we initially tested to determine if CD24 regulates lipid accumulation by regulating glucose uptake in adipocytes in vitro. We observed that instead, CD24 caused the dysregulation of the expression of 134 genes as determined by DNA microarray analysis. We then validated the expression of select four genes, when CD24 is knocked down during the different stages of adipogenesis in 3T3-L1 pre-adipocytes in vitro. To further confirm the role of these genes, we then determined the expression patterns of these four genes in primary cells undergoing adipogenesis that were isolated from the epididymal and inguinal white adipose tissue depots of CD24 knockout mice. Surprisingly, we found that these genes were dysregulated in the inguinal but not the epididymal depot in vitro. Overall, the data presented here suggests that CD24 is necessary for select gene expression, but not glucose uptake, during adipogenesis in vitro.
CD24 is required for regulating gene expression, but not glucose uptake, during adipogenesis.
Cell line
View SamplesAsthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP.
Gene transcription changes in asthmatic chronic rhinosinusitis with nasal polyps and comparison to those in atopic dermatitis.
Specimen part, Disease, Disease stage
View SamplesWe sorted Eomes-negative NK cells (CD3- CD56+ CXCR6- CD16-) and Eomes-positive NK cells (CD3- CD56+ CXCR6+) from total leukocytes isolated from the perfusion fluid of five healthy human livers destined for transplantation. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed. Overall design: Examination of mRNA levels in paired Eomes-negative/Eomes-positive NK cells from the same donor.
Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.
Specimen part, Subject
View SamplesWe used heterokaryon cell fusion based reprogramming and identified the cytokine IL6 as a potential regulator of reprogramming to pluripotency. We generated iPS clones using the four reprogramming factors (4F) Oct4, Klf4, Sox2, and c-Myc. In addition, iPS clones were generated using only three factors (3F: Oct4, Klf4, amd Sox2) with the addition of the cytokine IL6 to reprogramming culture conditions. Global RNA-Seq of the 3F + IL6 derived iPS clones was done for comparison with 4F-derived iPS clones, mouse embryonic stem cells and mouse embryonic fibroblasts. Overall design: This study includes 8 samples: 2 independently derived 3F + IL6 iPS clones, 2 independently derived 4F iPS clones, 2 biological replicates of mouse D3-GFP ES cells, and 2 biological replicates of mouse embryonic fibroblasts (MEFs). The latter 6 samples are provided as references for the 3F + IL6 iPS clones. Poly-A RNA was isolated and prepared for sequencing using the Illumina TruSeq RNA kit (v2) to generate 50bp reads. Reads were aligned to mm10.
NKX3-1 is required for induced pluripotent stem cell reprogramming and can replace OCT4 in mouse and human iPSC induction.
Specimen part, Treatment, Subject
View SamplesAntibody-independent effector functions of B cells, such as antigen presentation and cytokine production, have been shown to play an important role in a variety of immune-mediated conditions such as autoimmune diseases, transplant rejection and graft-versus-host disease. Therapeutic strategies, which interfere with B cell activation could therefore be a useful addition to the current immunosuppressive armamentarium. CD40 is one of the strongest activation stimuli for B cells. The aim of this study was to characterise the gene expression changes that occurr after B cell activation via CD40.
Inhibition of protein geranylgeranylation specifically interferes with CD40-dependent B cell activation, resulting in a reduced capacity to induce T cell immunity.
Specimen part, Subject
View Samples