In this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Gene expression analysis show downregulation of genes involved in oxidative phosphorylation (OXPHOS) upon loss of p53. In addition, p53KD neural stem cells upregulate genes involved in neuronal differentiation and display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Taken together, this demonstrates an important role for p53 in controlling genomic stability of neural stem cells and regulation of neuronal differentiation.
p53 controls genomic stability and temporal differentiation of human neural stem cells and affects neural organization in human brain organoids.
Specimen part
View SamplesNaïve CD4 T cells differentiate into functionally diverse subsets of T helper (Th) cells. Gene expression profiling has the capacity to pinpoint factors that regulate subset differentiation and function, however obtaining transcriptional profiles of pure populations has been challenging. We performed single cell RNA-Sequencing (scRNA-Seq) of T helper cells from lymph node, lung and airways in a mouse model of asthma. scRNA-Seq resolved transcriptional profiles of naïve CD4 T, Th1, Th2, Treg cells and various activated states including a population responding to type I interferons. A trajectory for Th2 cell differentiation was delineated over time, with Th2 cells acquiring follicular T helper cell characteristics in the lung-draining lymph node before undergoing further modifications in the lung. A feature of airway Th2 cells was their enrichment for genes associated with lipid metabolism and experiments with blockers of key metabolic pathways supported roles for glucose and lipid metabolism in Th2 cell differentiation. Overall design: Mice were sentized and challanged with HDM extract intranasally. scRNA-Seq was performed in 384-well format. The relevant organs (either BAL, lung or mLN) were isolated, rapidly processed, stained for a panel of surface markers and single cell sorted within approximately 90 minutes of organ harvest. In total 764 memory T helper cells (CD3+CD4+CD44+) were sorted directly into lysis buffer using a BD Influx from two independent mice 15 days after sensitization and challenge with HDM as described above. In addition, 50 naïve T Helper cells (CD3+CD4+CD62LhiCD44lo), 50 Treg cells (CD3+CD4+CD25hi) from mLN of a mouse not exposed to HDM; 200 ST2+ mLN and 82 ST2+ lung T helper cells (CD3+CD4+CD44+ST2+CD25-) were sort purified at day 10 of the HDM model. SMART-Seq2 libraries were prepared using the method described in Picelli et al. (Nature Methods 2013) by the Eukaryotic Single Cell Genomics national facility at SciLife Laboratory, Stockholm.
Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.
Specimen part, Subject
View SamplesAortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV) which results in dilation, eccentric hypertrophy and eventually loss of function. Little is known about the impact of AR on LV gene expression. We therefore conducted a gene expression profiling study in the LV of male Wistar rats with chronic (9 months) and severe AR.
Multiple short-chain dehydrogenases/reductases are regulated in pathological cardiac hypertrophy.
Sex
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The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice.
Specimen part
View SamplesThe t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion.
The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice.
Specimen part
View SamplesBrains are sexually dimorphic in adult zebrafish. We dissected brains from young and old, adult zebrafish, from both males and females.
Gene expression changes in aging zebrafish (Danio rerio) brains are sexually dimorphic.
Specimen part
View SamplesThe purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents that changed expression in response to the burrowing of live scabies mites.
Sarcoptes scabiei mites modulate gene expression in human skin equivalents.
Specimen part, Treatment
View Samplesob/ob mice is an obese mice. CIDE family proteins including Cidea, Cideb and Cidec play important role in lipid metabolism. Cidea is mainly expressed in the brown adipose tissue (BAT). Cidec is mainly expressed in the BAT and white adipose tissue (WAT). We generated ob/ob/Cidea-/-/Cidec-/- mice to investigate the phenotype of fat tissue. ob/ob/Cidea-/-/Cidec-/- mice are lean when compared with ob/ob mice. The tissue weight and TAG content of BAT and WAT was extreamly decreased in ob/ob/Cidea-/-/Cidec-/- mice compared with that in ob/ob mice.
Coordination Among Lipid Droplets, Peroxisomes, and Mitochondria Regulates Energy Expenditure Through the CIDE-ATGL-PPARα Pathway in Adipocytes.
Sex, Age, Specimen part
View SamplesUsing Affymetrix microarray technology we analyzed the gene expression profiles of the most important pathological categories of bladder cancer in order to detect potential marker genes. Applying an unsupervised cluster algorithm we observed clear differences between tumor and control samples, as well as between superficial and muscle invasive tumors. According to cluster results, the T1 high grade tumor type presented a global genetic profile which could not be distinguished from invasive cases. We described a new measure to classify differentially expressed genes and we compared it against the B-rank statistic as a standard method. According to this new classification method, the biological functions overrepresented in top differentially expressed genes when comparing tumor versus control samples were associated with growth, differentiation, immune system response, communication, cellular matrix and enzyme regulation. Comparing superficial versus invasive samples, the most important overrepresented biological category was growth and, specifically, DNA synthesis and mitotic cytoskeleton. On the other hand, some under expressed genes have been clearly related to muscular tissue contamination in control samples. Finally, we demonstrated that a pool strategy could be a good option to detect the best differentially expressed genes between two compared conditions.
DNA microarray expression profiling of bladder cancer allows identification of noninvasive diagnostic markers.
No sample metadata fields
View SamplesWe used microarrays to expression profile peripheral blood mononuclear cells (PBMCs) from LGL leukemia patients and control subjects to identify survival pathways that render leukemic LGL resistant to activation induced cell death.
Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes.
No sample metadata fields
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