The role of topographic cues in controlling commitment of induced pluripotent stem cells (iPSCs) is largely unknown. Here we demonstrate that groove-ridge nanostructures induce the elongation of iPSC colonies, guide the orientation of apical actin fibers and direct the polarity of cell division. Elongation of iPSC colonies impacts also on the intrinsic molecular patterning which seems to be orchestrated starting from the rim of the colonies. We followed the hypothesis that nanotopography directly modulates the transcriptional program of iPSC, further to guiding the overall spatial organization of the colonies. Single iPSC were seeded on flat (PI flat) and nanostructured polyimide (PI 650) and gene expression profiles were analyzed after three days. No significant differences were observed when cells were kept under culture conditions that sustained pluripotency. Then, we analyzed gene expression changes upon two weeks of multi-lineage differentiation. Many genes revealed significant expression changes in the course of differentiation and this was more pronounced on PI flat as compared to PI 650. Comparison of iPSC that were either differentiated on flat or nanostructured biomaterials revealed differential expression of several genes. Noteworthy, among significantly regulated genes, the biggest fold change on PI 650 versus PI flat after differentiation was observed in ANKRD1, which is one of the best readouts of YAP/TAZ activity. Our study suggests that nanotopography impacts on orientation and organization of iPSC colonies and highlight a possible interaction between mechanosensors and mechanotransducers.
Surface Topography Guides Morphology and Spatial Patterning of Induced Pluripotent Stem Cell Colonies.
Specimen part, Subject
View SamplesThe transcription factor STAT1 is essential for interferon- (IFN) mediated protective immunity in humans and mice. Two splice isoforms of STAT1, STAT1 and STAT1, differ with regard to a C-terminal transactivation domain, which is absent in STAT1. Dimers of STAT1 are therefore considered transcriptionally inactive and potential competitive inhibitors of STAT1. Contrasting this view, generation and analysis of mice deficient for either STAT1 or STAT1 demonstrated transcriptional activity of the STAT1 isoform and its enhancement of innate immunity. Gene expression profiling in primary cells revealed overlapping, but also non-redundant and gene-specific activities of STAT1 and STAT1 in response to IFN. Consistently, both isoforms mediated protective, IFN-dependent immunity against the bacterium Listeria monocytogenes, although with remarkably different efficiency. In contrast, STAT1 and STAT1 were largely redundant for transcriptional responses to IFN/ and for IFN/-dependent antiviral activity. Collectively, our data shed new light on how STAT1 isoforms contribute to antimicrobial immunity.
STAT1β is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity.
Specimen part
View SamplesDetermining which genes are expressed in mechanoreceptor-rich tissue (pedicel) compared mechanoreceptor-poor tissue (capitellum) and a neuronal subtraction control (thoracic ganglion) in Drosophila melanogaster
A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia.
Sex, Age, Specimen part
View SamplesBackground: Peripheral blood mononuclear cells (PBMCs) are relatively easily obtainable cells in humans. Gene expression profiles of PBMCs have been shown to reflect the pathological and physiological state of a person. Recently, we showed that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR) has a functional role in human PBMCs during fasting. However, the extent of the role of PPAR in human PBMCs remains unclear. In this study, we therefore performed gene expression profiling of PBMCs incubated with the specific PPAR ligand WY14,643. Results: Incubation of PBMCs with WY14,643 for 12 hours resulted in a differential expression of 1,373 of the 13,080 genes expressed in the PBMCs. Gene expression profiles showed a clear individual response to PPAR activation between six healthy human blood donors, which was not the result of the nutritional status of the donors. Pathway analysis showed that genes in fatty acid metabolism, primarily in -oxidation were up-regulated upon activation of PPAR with WY14,643, and genes in several amino acid metabolism pathways were down-regulated. Conclusions: This study shows that PPAR in human PBMCs regulates fatty acid and amino acid metabolism. In addition, PBMC gene expression profiles show individual responses to WY14,643 activation. We show that PBMCs are a suitable model to study changes in PPAR activation in healthy humans.
Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response.
No sample metadata fields
View SamplesMicroarray analyses provide a powerful approach to identify gene expression alterations following kidney transplantation. However, the heterogeneity of human kidney transplant specimens and the variation in sample preparation precludes conclusions regarding the underlying mechanisms of the observed alterations. We used a well defined experimental rat kidney transplantation model with consistent transplant and sample preparation procedures to analyze genome wide changes in gene expression after syngeneic (sTX) and allogeneic transplantation (aTX) four days after transplantation. Both interventions were associated with dramatic changes in gene expression. Genes and Pathways related to immune response were extremely up regulated after aTX. Several of the up regulated genes have been described by other groups and we are able to proof this in one study. But several genes are reported for the first time to be up regulated in expression after renal aTX. The function of these genes in acute rejection process has to be evaluated. On the other hand the up regulation of regulatory or protective genes indicates that regulatory mechanism are activated after aTX trying to down regulate the immune response or protect the tissue against the immune system. The study is capable to serve as a representative study in aTX mediated gene expression by covering the known transcriptional changes reported by other groups and identification of novel markers and pathways. Further analysis of the duplicated datasets by other groups can help for a better understanding of the mechanisms mediated by acute rejection and thereby increase the therapeutic threatment.
Activation of counter-regulatory mechanisms in a rat renal acute rejection model.
No sample metadata fields
View SamplesWe found the PRC2 component EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in Ewing tumors and mesenchymal stem cells (Richter GH et al., Proc Natl Acad Sci U S A. 2009;106:5324-9). Downregulation of EZH2 by RNA interference in Ewing tumor cell lines suppressed oncogenic transformation in vitro and in vivo. These data suggest that EZH2 might play a central role in Ewing Tumor pathology.
Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.
Specimen part, Cell line
View SamplesHere, we analyzed global gene expression changes that were associated with drug resistance in Acute Myeloid Leukemia using the Affymetrix microarray platform.
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sex, Treatment
View SamplesFatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid. Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPAR/ mice to allow exploration of the specific contribution of PPAR. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPAR agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPAR-dependent manner, emphasizing the importance of PPAR in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPAR had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPAR.
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sex, Treatment
View Samples