Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability.
A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets.
Sex, Age, Specimen part
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 SamplesWe 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 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 SamplesAffymetrix Mouse Genome 430 2.0 arrays were used to measure genome-wide gene expression levels. The results show that high-risk human papillomavirus oncogenes E6 and E7 reprogram the cervical cancer microenvironment independently of and synergistically with estrogen, a critical co-factor in cervical cancer development and maintenance.
Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen.
Specimen part, Treatment
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 SamplesNasopharyngeal carcinoma is an Epstein-Barr virus-associated epithelial cancer with high prevalence in Southeast Asia. mRNA expression levels were measured for essentially all human genes and all latent Epstein-Barr virus (EBV) genes in nasopharyngeal carcinoma tissue samples and normal nasopharyngeal tissues. Data were analyzed for differential gene expression between tumor and normal tissue and for correlations with levels of viral gene expression. Primary publications: Sengupta et al, 2006, Cancer Research 66(16): 7999-8006. Dodd et al, 2006, Cancer Epidemiology, Biomarkers & Prevention 15(11): 2216-2225.
Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma.
No sample metadata fields
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