BACKGROUND: Dendritic cells (DC) play a central role in primary immune responses and become potent stimulators of the adaptive immune response after undergoing the critical process of maturation. Understanding the dynamics of DC maturation would provide key insights into this important process. Time course microarray experiments can provide unique insights into DC maturation dynamics. Replicate experiments are necessary to address the issues of experimental and biological variability. Statistical methods and averaging are often used to identify significant signals. Here a novel strategy for filtering of replicate time course microarray data, which identifies consistent signals between the replicates, is presented and applied to a DC time course microarray experiment.
Dynamics of dendritic cell maturation are identified through a novel filtering strategy applied to biological time-course microarray replicates.
Specimen part
View SamplesAuxin-dependent transcript abundance was assayed by transferring 6 day old Arabidopsis grown on a a nylon mesh to IAA-containing or control media
A kinetic analysis of the auxin transcriptome reveals cell wall remodeling proteins that modulate lateral root development in Arabidopsis.
Specimen part
View SamplesThe purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint organ and analyzed using microarrays.427 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin.The results support a phasic development of OA with early matrix remodelling and transcriptional activity followed by a more quiescent period that is not maintained.
Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis.
Sex, Age, Specimen part
View SamplesForkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. Foxd1 is required during kidney development and its inactivation results in failure of nephron progenitor cell differentiation. Foxd1 is expressed in interstitial cells adjacent to nephron progenitor cells, suggesting an essential role for the progenitor cell niche in nephrogenesis. To better understand how cortical interstitial cells in general, and FOXD1 in particular, influence the progenitor cell niche, we examined the differentiation states of two progenitor cell subtypes in Foxd1-/- tissue. We found that while nephron progenitor cells are retained in a primitive CITED1-expressing compartment, cortical interstitial cells prematurely differentiate. To identify pathways regulated by FOXD1, we used microarray analysis and screened for target genes by comparison of Foxd1 null and wild type tissues.
FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney.
Specimen part
View SamplesHuman induced pluripotent stem (hiPS) cells and human embryonic stem (hES) cells differentiate into cells of the endothelial lineage, but derivation of cells with human umbilical cord blood endothelial colony forming cell (ECFC)-like properties has not been reported. Here we describe a novel serum- and stromal cell-free ECFC differentiation protocol for the derivation of clinically relevant numbers of ECFCs (> 108) from hiPS and hES cells. We identified NRP-1+CD31+ selected cells that displayed a stable endothelial phenotype exhibiting high clonal proliferative potential, extensive replicative capacity, formation of human vessels that inosculated with host vasculature upon transplantation, but lacking in teratoma formation in vivo. We also identified NRP-1-VEGF165-KDR-mediated activation of KDR as a critical mechanism for the emergence and derivation of ECFCs from hiPS and hES cells. This protocol advances the field by generating highly replicative but stable endothelial cells for use as a potential cell therapy for human clinical disorders. Overall design: Transcriptome sequencing of undifferentiated day 0 hiPS cells, Day 3 differentiated hiPS-derived mesoderm proginator cells, Day 12 hiPS-derived NRP-1+CD31+ cells, Day 12 H9-hES-derived NRP-1+CD31+ cells and cord blood-derived Endothelial colony forming cells.
Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer.
Specimen part, Cell line
View SamplesDiabetes is a complex metabolic syndrome characterized by prolonged high blood glucose levels. It is known that diabetes is associated with an elevated risk of cancer, however, the underlying molecular mechanisms are largely unknown. In particular, it remains unclear as to how hyperglycemia may affect epigenetic checkpoints and tumor suppressor pathways, thus enabling oncogenic transformation. Here we show that long-term hyperglycemic conditions adversely impact the anti-tumor epigenetic mark DNA 5-hydroxymethylcytosine (5hmC) through direct regulation of the tumor suppressor and DNA 5mC hydroxymethylase, TET2. We identify TET2 as a novel substrate of the AMP-activated kinase (AMPK).
Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer.
Specimen part, Cell line
View Samples