The intestine is an organ with exceptionally high rate of cell turnover and perturbations in this process can lead to disease such as cancer or intestinal atrophy. Nutrition is a key factor regulating the intestinal cell turnover and has a profound impact on intestinal volume and cellular architecture. However, how the intestinal equilibrium is maintained in fluctuating dietary conditions is insufficiently understood. By utilizing the Drosophila midgut as a model, we reveal a novel nutrient sensing mechanism coupling stem cell metabolism with stem cell extrinsic growth signal. Our results show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway (HBP) to monitor nutritional status and energy metabolism. Elevated activity of the HBP promotes Warburg effect-like metabolic reprogramming, which is required for the reactivation of ISCs from calorie restriction-induced quiescence. Furthermore, the HBP activity is an essential facilitator for insulin signaling-induced intestinal growth. In conclusion, intestinal stem cell intrinsic nutrient sensing regulates metabolic pathway activities, and defines the stem cell responsiveness to niche-derived growth signals. Overall design: Intestinal mRNA profiles of 7 days old mated females of UAS-mCD8::GFP, hsFLP; tub-GAL4/+; FRT82B tub-GAL80/FRT82B genotype kept in calorie-restriction +/- 0.1M D-acetylglucosamine for 24h.
Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content.
Sex, Specimen part, Treatment, Subject
View SamplesIn mouse, spermatogonial stem/progenitor cells are the progenitor cell which develop to mature sperms through a series of mitotic and meiotic divisions and differentiation. Gfra1 is an established surface marker for mouse spermatogonial stem/progenitor cells. In this study, we used a transcriptomic approach to investigate the effect of aging on Gfra1-positive and -negative populations of mouse male germ cells.
Age affects gene expression in mouse spermatogonial stem/progenitor cells.
Sex, Age
View SamplesPpargc1a overexpression in heart tissue measured using RNA sequencing Overall design: RNA expression profiles were generated using RNA-seq from control (N=3) and Ppargc1a overexpressing (N=3) mice
Peroxisome proliferator-activated receptor-γ coactivator 1 α1 induces a cardiac excitation-contraction coupling phenotype without metabolic remodelling.
Specimen part, Treatment, Subject
View SamplesCharacterization of the underlying genetic defects in patients with a rare and peculiar phenotype is challenging. Here we have utilized whole genome expression profiling, and identified a homozygous germline mutation in the DDB2 gene in a patient with several facial tumors. The feasibility of using blood derived RNA, diminishing costs of the technology, and the limited number of samples needed provide this approach a powerful new tool that may substantially aid in such gene identification efforts.
Blood-derived gene-expression profiling in unravelling susceptibility to recessive disease.
No sample metadata fields
View SamplesBoth environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Liver samples were extracted and hybridized to Affymetrix Genome U74 (version 2) arrays.
Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome.
Sex, Age, Specimen part
View SamplesThe character of the earliest cardiac precursor cells remains largely unknown. To elucidate this further, we constructed single cell cDNAs from the mouse embryonic cardiac precurcsor cells of the early allantoic bud stage and the early headfold stage, and subjected them to deep sequencing. Overall design: The most anterior part of the embryos where cardiac precursor cells exist was digested by trypsin to separate into single cells. After a cell was transferred into a reaction tube, single cell cDNAs were constructed as PCR amplicons. cDNAs of cardiac precursor cells were identified by PCR of marker genes.
Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
No sample metadata fields
View SamplesIn contrast to urodele amphibians and teleost fish, mammals lack the regenerative responses to replace large body parts. Amphibian and fish regeneration uses dedifferentiation, i.e. reversal of differentiated state, as a means to produce progenitor cells to eventually replace damaged tissues. Therefore, activation of dedifferentiation response in mammalian tissues holds an immense promise for human regenerative medicine. msx2 expression has been shown to peak at the early time points of amphibian limb regeneration. Despite this temporal importance in the heterogenous regenerating limb tissues, the potential role of msx2 in dedifferentiation was previously not addressed in salamander or mammalian muscle cells. In order to test this, we ectopically overexpressed msx2 in mammalian myotubes and profiled their transcriptomes using next generation sequencing. We identified 4964 up-regulated and 4464 down-regulated transcripts in myotubes compared to myoblasts (uninduced GFP control cells; = 1.5 fold; FDR corrected p-values < 0.01). Upon ectopic msx2 expression in myotubes, 923 transcripts were downregulated, whereas 1283 transcripts were upregulated. Based on msx2's potential role in dedifferentiation, we reasoned that the transcripts, which are normally upregulated in myotubes in comparison to myoblasts, should go down upon msx2-expression. In accord with this idea, 575 myotube-enriched transcripts were downregulated after one day of ectopic msx2 expression. Similarly, 331 myoblast-enriched transcripts were upregulated upon msx2 expression. Overall design: To extensively analyze transcriptome-wide changes upon ectopic msx2 expression in mammalian myotubes, we performed next generation RNA-sequencing (RNA-seq) on uninduced and induced isolated myotubes that have msx2 and GFP or GFP alone transgenes. As a reference for the undifferentiated state, we also sequenced the transcriptomes of uninduced myoblast cultures of these two transgenic constructs. Deep sequencing was performed using Illumina HiSeq.
Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation.
No sample metadata fields
View SamplesWe are daily exposed to a multitude of health hazardous airborne particulate matter with notable deposition in the fragile alveolar region of our lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modelling, we have here determined that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows us to predict the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modelling potentially relating outcomes to material properties for large number of materials thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, our work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives.
Prediction of Chronic Inflammation for Inhaled Particles: the Impact of Material Cycling and Quarantining in the Lung Epithelium.
Cell line
View SamplesEffect of fumarase point mutation or knock-out on transcriptional profile in yeast to model hereditary leiomyomatosis and renal cell cancer (HLRCC).
Modeling tumor predisposing FH mutations in yeast: effects on fumarase activity, growth phenotype and gene expression profile.
Sex, Subject
View SamplesSerrated adenocarcinomas are morphologically different from conventional adenocarcinomas. The serrated pathway has recently been proposed to represent a novel mechanism of colorectal cancer (CRC) formation. However, whether they are biologically different and truly form a distinct subclass of CRC, is not known. This study shows that the gene expression profile of serrated and conventional CRCs differs from each others and that serrated CRCs are not only morphologically novel, but also biologically distinct subclass of CRC.
Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.
No sample metadata fields
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