We used microarrays to detail the global program of gene expression underlying Parkinson's disease
A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.
No sample metadata fields
View SamplesLoss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
Cell intrinsic alterations underlie hematopoietic stem cell aging.
No sample metadata fields
View SamplesThe tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells -- including inhibition of the mitochondrial ribosome -- there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation and alter cell cycle progression in vitro. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.
Doxycycline alters metabolism and proliferation of human cell lines.
Specimen part, Cell line, Treatment
View SamplesWe report the generation of induced oligodendrocyte precursor cells (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to convert mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures that resemble OPCs.
Generation of oligodendroglial cells by direct lineage conversion.
Specimen part
View SamplesIn a randomized controlled dietary intervention study, we compared a diet enriched in polyunsaturated fatty acids (PUFA) with a diet enriched in saturated fatty acids (SFA) for influence on abdominal subcutaneous adipose tissue gene expression. We studied young lean adults; 11 women and 25 men. There was no significant difference in age, BMI, or gene expression between the PUFA and SFA groups before the intervention. The intervention lasted for seven weeks.
Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans.
Sex, Age, Specimen part, Treatment, Subject, Time
View SamplesGroucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. A pro-oncogenic potential for GRG5 is revealed by the malignant behavior of teratomas generated from ESCs that overexpress it. Furthermore, transcriptomic analysis and cell differentiation approaches underline GRG5 as a multifaceted signaling regulator that represses mesendodermal-related genes. When ES cells exit pluripotency, GRG5 promotes neuroectodermal specification via Wnt and BMP signaling pathways suppression. Moreover, GRG5 promotes the neuronal reprogramming of fibroblasts and maintains the self-renewal of Neural Stem Cell (NSC) by sustaining the activity of Notch and Jak/Stat3 pathways. In summary, our results demonstrate that GRG5 has pleiotropic roles in stem cell biology functioning as a stemness factor and a neural fate specifier. Overall design: Gene expression profiling of control and Grg5 knockdown (KD) embryonic stem cells with RNA-seq, in dublicate, using Ion Torrent Proton.
Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions.
Cell line, Subject
View SamplesPBMC from house dust mite (HDM) sensitized atopics were cultured in the presence or absence of HDM extract for 24 hours.
Distinguishing benign from pathologic TH2 immunity in atopic children.
No sample metadata fields
View SamplesWe report RNA Seq analysis using Illumina nextSeq500 of human beta cells EndoC-BH1 treated with FGF2 to induce dedifferentiation. FGF2 treatment induced dedifferentiation of EndoC-BH1 cells. Indeed, we observed a strong decrease in expression of ß-cell markers, (INS, MAFB, SLC2A2, SLC30A8 and GCK). Opposingly, we identifed positive markers of human ß cell dedifferentiation, as attested by increased expression of mature ß-cell disallowed transcription factors (MYC, HES1, SOX9 and NEUROG3). Interestingly, our temporal analysis revealed that loss of expression of ß cell specific markers preceded the induction of ß cell disallowed genes. Overall design: human beta cells EndoC-BH1 were treated with FGF2 (100ng/L) during 4, 24, 72 and 144h. RNA was isolated post treatment, along with the non-treated controls, and RNA Seq was performed using Illumina nextSeq500 to generate a full transcriptome analysis of gene expression during dedifferentiation of pancreatic beta cells.
Modeling human pancreatic beta cell dedifferentiation.
Specimen part, Cell line, Subject, Time
View SamplesGene expression profiling on IL-10-secreting and non-secreting murine Th1 cells, stimulated in the presence or absence of the Notch ligand Delta-like 4 (Dll4), was performed to identify transcription factors co-expressed with IL-10.
Role of Blimp-1 in programing Th effector cells into IL-10 producers.
Specimen part
View SamplesBackground/Aims: Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C. Methods: 70 treatment-nave patients were randomized to 4 weeks of ribavirin (1000-1200 mg/d) or none, followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were randomized to undergo a liver biopsy either 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by the nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10. Results: After four weeks of ribavirin monotherapy, HCV levels decreased by 0.50.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting the induction of ISGs by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC. Conclusion: Ribavirin is a weak antiviral but its clinical effect in combination with PEG-IFN seems to be mediated by a separate, indirect mechanism, which may act to reset the interferon responsiveness in HCV-infected liver. Ribavirin pretreatment does not alter the clinical outcome of subsequent combination therapy.
Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C.
Specimen part, Disease, Disease stage, Treatment
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