We comprehensively explored Fas expression (protein and mRNA) and function in lymphocyte activation, apoptosis, proliferation and transcriptome, using flow cytometry, [3H]-thymidine incorporation and microarray analysis in PBMC from HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) patients.
A Fas<sup>hi</sup> Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.
Specimen part, Disease stage, Treatment
View SamplesEndodermal progenitor cells (EP cells) are derived from human embryonic stem cell(ESC)-derived definitive endoderm (DE) cells. EP cells are cultured in high BMP media and DE cells are in high Activin media. Both cells can be further differentiated to liver, pancreas, etc.
Self-renewing endodermal progenitor lines generated from human pluripotent stem cells.
Specimen part
View SamplesA mRNA expression study has been performed 20-25 minutes postmortem obtained samples from Longissimus dorsi muscle of 59 Duroc x LD/LW pigs to search for gene sequences related to meat quality (pH24, pH45, Lab colour coordinates, curing yield and exudation at three different times) or to meat composition (intramuscular fat, content of several fatty acid (C16:0, C18:0, C18:1 and C18:2), ratio of saturated, monounsaturated and polyunsaturated fatty acids, and protein and humidity contents) traits in order to find targets for selection. Gene ontology analysis, biological pathways and gene networks studies all show, that many more differentially expressed genes (506 vs 279) are related to meat quality (Group P, or perimortem characters) than to meat composition traits (Group L, or whole life traits). The difference between the number of GO terms annotated, biological pathways and gene networks in groups P and L is notable due to the differences in the complexity of the generation process of P-traits and the involvement of other tissues or organs in the generation of variability of L-traits. Also, interactions between a list of differentially expressed genes were found in ECM-receptor interaction, TGF-beta signaling pathway, fatty acid elongation in mitochondria and adipocytokine signalling pathway indicating that a substantial fraction of the gene networks could be associated with interactions between differential expressed genes related to traits under study. A high number of the most overexpressed genes are related to muscle development and functionality and repair mechanisms; they could be good candidates for breeding programs whose main goal is to enhance meat quality.
Early postmortem gene expression and its relationship to composition and quality traits in pig Longissimus dorsi muscle.
Age, Specimen part
View SamplesInduced pluripotent stem cells hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained.
Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines.
Specimen part, Cell line
View SamplesTumor cells utilize the so-called Warburg effect to allow for rapid proliferation with glucose as the main nutrient. We show here that, although PKCz is critical for that effect, its deficiency promotes the plasticity necessary for nutrient-stressed cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway, empowering them to survive and proliferate in the absence of glucose. We show that PKCz deficiency enhances glutamine utilization and expression of two key enzymes of the pathway, PGHDGH and PSAT1, in cells cultured in the absence of glucose. The loss of PKCz in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, while patients with low levels of PKCz have a poor prognosis. Taken together, this suggests that PKCz is a critical metabolic tumor suppressor.
Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis.
Cell line, Treatment
View SamplesAIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment, thus constituting a good genetic model to investigate differences in gene expression profiles related to inflammatory response and lung tumor susceptibility. The transcript profile of ~24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation associated genes involved in pathways such as leukocyte transendothelial migration, cell adhesion and tight junctions were differentially expressed in AIRmax versus AIRmin mice. Moreover, gene expression levels differed significantly in urethane-treated mice even at 21 days after treatment. In AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice. In conclusion, a specific gene expression profile in normal lung tissue is associated with mouse line susceptibility or resistance to lung tumorigenesis and with different inflammatory response, and urethane treatment causes a long-lasting alteration of the lung gene expression profile that correlates with persistent inflammatory response of AIRmin mice.
Transcriptome of normal lung distinguishes mouse lines with different susceptibility to inflammation and to lung tumorigenesis.
Sex, Specimen part
View SamplesFibroblasts from patients with Type I bipolar disorder (BPD) and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs). Established iPSCs were subsequently differentiated into neuroprogenitors (NPs) and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (termed late neurons, L). Global RNA profiling indicated that BPD and control iPSCs differentiated into NPs and neurons at a similar rate, enabling studies of differentially expressed genes in neurons from controls and BPD cases. Significant disease-associated differences in gene expression were observed only in L neurons. Specifically, 328 genes were differentially expressed between BPD and control L neurons including GAD1, glutamate decarboxylase 1 (2.5 fold) and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold). Quantitative RT-PCR confirmed the up-regulation of GAD1 in BPD compared to control L neurons. Gene Ontology, GeneGo and Ingenuity Pathway Analysis of differentially regulated genes in L neurons suggest that alterations in RNA biosynthesis and metabolism, protein trafficking as well as receptor signaling pathways GSK3 signaling may play an important role in the pathophysiology of BPD.
Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.
Specimen part, Cell line
View SamplesThe de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methylase that has been previously shown to cooperate with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESC) but its function in these cells is unknown. We here report that Dnmt3L is required for the differentiation of ESC into primordial germ cells (PGC) through activation of the homeotic gene Rhox5. By genome-wide analysis we found that Dnmt3L is a positive regulator of methylation at gene bodies of housekeeping genes and a negative regulator of methylation at promoters of bivalent genes. We demonstrate that Dnmt3L interacts with the Polycomb PRC2 complex in competition with the DNA methyl transferases Dnmt3a and Dnmt3b to maintain low the methylation level at H3H27me3 regions. Thus in ESC, Dnmt3L counteracts the activity of de novo DNA methylases to keep low the level of DNA methylation at developmental gene promoters.
Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.
Specimen part
View SamplesAdult mammalian CNS neurons undergo a developmental switch in intrinsic axon growth ability associated with their failure to regenerate axons after injury. Krppel-like transcription factors (KLF) regulate intrinsic axon growth ability, but signaling regulation upstream and downstream is poorly understood. Here we find that suppressing expression of KLF9, an axon growth suppressor normally upregulated 250-fold in retinal ganglion cell (RGC) development, promotes long-distance optic nerve regeneration in vivo. We identify a novel binding partner, MAPK10/JNK3, critical for KLF9s axon growth suppressive activity. Additionally, by screening genes regulated by KLFs in RGCs, we identify dual-specificity phosphatase 14 (Dusp14) as key to limiting axon growth and regenerative ability downstream of KLF9, associated with its dephosphorylation of MAPKs critical to neurotrophic signaling of RGC axon elongation. These results now link intrinsic and extrinsic regulation of axon growth and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.
The Krüppel-Like Factor Gene Target Dusp14 Regulates Axon Growth and Regeneration.
Specimen part
View Samples