Huntingtons disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons under defined culture conditions. Analysis of differentially expressed genes between Huntingtons disease and wild type iPSCs derived GABA MS-like neurons has been performed.
Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons.
Age, Specimen part
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Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF.
Specimen part, Treatment, Time
View SamplesWe examine the global effect of hBD3 on transcription in TLR4-stimulated macrophages and for the first time show that hBD3 inhibits the transcription of critical pro-inflammatory genes.
Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF.
Specimen part, Treatment, Time
View SamplesGene expression profiling for identification of genes regulated by DNA methylation
Genome-wide screening of genes regulated by DNA methylation in colon cancer development.
Specimen part, Cell line
View SamplesActivation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia. We found that HIF-1 also actively suppresses glucose metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1-null cells increases ATP levels, attenuates hypoxic ROS generation and rescues these cells from hypoxia-induced apoptosis. These studies reveal a novel hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production.
HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.
No sample metadata fields
View SamplesGene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measured the gene expression dynamics of retinoic acid driven mESC differentiation using an unbiased single-cell transcriptomics approach. We found that the exit from pluripotency marks the start of a lineage bifurcation as well as a transient phase of susceptibility to lineage specifying signals. Our study revealed several transcriptional signatures of this phase, including a sharp increase of gene expression variability and a handover between two classes of transcription factors. In summary, we provide a comprehensive analysis of lineage commitment at the single cell level, a potential stepping stone to improved lineage control through timing of differentiation cues. Overall design: Bulk and single-cell RNA-seq (SCRB-seq and SMART-seq) of mouse embryonic stem cells after different periods of continuous exposure to retinoic acid. Bulk RNA-seq of cell lines derived after retinoic exposure and after differentiation with retinoic acid and MEK inhibitor combined.
Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells.
Cell line, Subject
View SamplesAbnormal development of the prefrontal cortex (PFC) is associated with a number of neuropsychiatric disorders that have an onset in childhood or adolescence. Although the basic laminar structure of the PFC is established in utero, extensive remodeling continues into adolescence. To map the overall pattern of changes in cortical gene transcripts during post-natal development, we made serial measurements of mRNA levels in mouse PFC using oligonucleotide microarrays. We observed changes in mRNA transcripts consistent with known post-natal morphological and biochemical events. Overall, most transcripts that changed significantly showed a progressive decrease in abundance after birth, with the majority of change between post-natal weeks 2 and 4. Genes with cell proliferative, cytoskeletal, extracellular matrix, plasma membrane lipid / transport, protein folding, and regulatory functions had decreases in mRNA levels. Quantitative PCR verified the microarray results for six selected genes: DNA methyltransferase 3A (Dnmt3a), procollagen, type III, alpha 1 (Col3a1), solute carrier family 16 (monocarboxylic acid transporters), member 1 (Slc16a1), MARCKS-like 1 (Marcksl1), nidogen 1 (Nid1) and 3-hydroxybutyrate dehydrogenase (heart, mitochondrial) (Bdh).
Microarray analysis of the developing cortex.
No sample metadata fields
View SamplesWe demonstrated that, four weeks after the pulmonary artery banding (PAB) operation, rats could be divided into two groups: an F+ group in which the fibrotic area occupied more than 6.5% of the whole area of the heart tissues, and an F- group in which the fibrotic area occupied less than 6.5% of this area.
Fibrosis growth factor 23 is a promoting factor for cardiac fibrosis in the presence of transforming growth factor-β1.
Sex, Specimen part
View SamplesThe new official nomenclature subdivides human monocytes into three subsets, classical (CD14++CD16-), intermediate (CD14++CD16+) and nonclassical (CD14+CD16+). Here, we comprehensively define relationships and unique characteristics of the three human monocyte subsets using microarray and flow cytometry analysis. Our analysis revealed that the intermediate and nonclassical monocyte subsets were most closely related. For the intermediate subset, majority of genes and surface markers were expressed at an intermediary level between the classical and nonclassical subset. There features therefore indicate a close and direct lineage relationship between the intermediate and nonclassical subset. From gene expression profiles, we define unique characteristics for each monocyte subset. Classical monocytes were functionally versatile, due to the expression of a wide range of sensing receptors and several members of the AP-1 transcription factor family. The intermediate subset was distinguished by high expression of MHC class II associated genes. The nonclassical subset were most highly differentiated and defined by genes involved in cytoskeleton rearrangement that explains their highly motile patrolling behavior in vivo. Additionally, we identify unique surface markers, CLEC4D, IL-13RA1 for classical, GFRA2, CLEC10A for intermediate and GPR44 for nonclassical. Our study hence defines the fundamental features of monocyte subsets necessary for future research on monocyte heterogeneity.
Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets.
Specimen part, Subject
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