Endothelium in embryonic hematopoietic tissues generates hematopoietic stem/progenitor cells; however, it is unknown how its unique potential is specified. We show that transcription factor Scl/Tal1 is essential for both establishing the hematopoietic transcriptional program in hemogenic endothelium and preventing its misspecification to a cardiomyogenic fate. Scl-/- embryos activated a cardiac transcriptional program in yolk sac endothelium, leading to the emergence of CD31+Pdgfr+ cardiogenic precursors that generated spontaneously beating cardiomyocytes. Ectopic cardiogenesis was also observed in Scl-/- hearts, where the disorganized endocardium precociously differentiated into cardiomyocytes. Induction of mosaic deletion of Scl in Sclfl/flRosa26Cre-ERT2 embryos revealed a cell-intrinsic, temporal requirement for Scl to prevent cardiomyogenesis from endothelium. Scl-/- endothelium also upregulated the expression of Wnt antagonists, which promoted rapid cardiomyocyte differentiation of ectopic cardiogenic cells. These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells.
Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium.
Specimen part
View SamplesThe MAQC-II Project: A comprehensive study of common practices for the development and validation of microarray-based predictive models
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sex, Age, Specimen part, Race, Compound
View SamplesThe Hamner data set (endpoint A) was provided by The Hamner Institutes for Health Sciences (Research Triangle Park, NC, USA). The study objective was to apply microarray gene expression data from the lung of female B6C3F1 mice exposed to a 13-week treatment of chemicals to predict increased lung tumor incidence in the 2-year rodent cancer bioassays of the National Toxicology Program. If successful, the results may form the basis of a more efficient and economical approach for evaluating the carcinogenic activity of chemicals. Microarray analysis was performed using Affymetrix Mouse Genome 430 2.0 arrays on three to four mice per treatment group, and a total of 70 mice were analyzed and used as the MAQC-II's training set (GEO Series GSE6116). Additional data from another set of 88 mice were collected later and provided as the MAQC-II's external validation set (this Series). The training dataset had already been deposited in GEO by its provider and its accession number is GSE6116.
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Specimen part, Compound
View SamplesInfection of RAW264.7 cells with RHku80 parasites or mock-infection for 24 hours
Infection by Toxoplasma gondii specifically induces host c-Myc and the genes this pivotal transcription factor regulates.
Cell line
View SamplesInfection of RAW264.7 cells for 24 hours with 32 Toxoplasma Progeny from a Type II x Type III cross
GRA25 is a novel virulence factor of Toxoplasma gondii and influences the host immune response.
No sample metadata fields
View SamplesOur present study reveals significant decelerating effects on senescence processes in middle-aged SAMP1 mice supplemented for 6 or 14 months with the reduced form (QH2, 500 mg/ kg BW/ day) of coenzyme Q10 (CoQ10). To unravel molecular mechanisms of these CoQ10 effects, a genome-wide transcript profiling in liver, heart, brain and kidney of SAMP1 mice supplemented with the reduced (QH2) or oxidized form of CoQ10 (Q10) was performed. Liver seems to be the main target tissue of CoQ10 intervention, followed by kidney, heart and brain. Stringent evaluation of the resulting data revealed that QH2 has a stronger impact on gene expression than Q10, which was primarily due to differences in the bioavailability. Indeed, we found that QH2 supplementation was more effective than Q10 to increase levels of CoQ10 in the liver of SAMP1 mice (54.92-fold and 30.36-fold, respectively). To identify functional and regulatory connections of the top 50 (p < 0.05) up- and down-regulated QH2-sensitive transcripts in liver (fold changes ranging from 21.24 to -6.12), text mining analysis (Genomatix BiblioSphere, GFG level B3) was used. Hereby, we identified 11 QH2-sensitive genes which are regulated by PPAR- and are primarily involved in cholesterol synthesis (e.g. HMGCS1, HMGCL, HMGCR), fat assimilation (FABP5), lipoprotein metabolism (PLTP) and inflammation (STAT-1). Thus, we provide evidence that QH2 is involved in the reduction of fat and cholesterol synthesis via modulation of the PPAR- signalling pathway. These data may explain, at least in part, the observed effects on decelerated age-dependent degeneration processes in QH2-supplemented SAMP1 mice.
Supplementation with the reduced form of Coenzyme Q10 decelerates phenotypic characteristics of senescence and induces a peroxisome proliferator-activated receptor-alpha gene expression signature in SAMP1 mice.
Sex, Age, Specimen part
View SamplesSusceptible and Resistant mouse strain, e.g. DBA/2J and C57BL/6J respectively, were inoculated with a highly pathogenic H5N1 influenza A virus (A/Hong Kong/213/2003) for 72 hours.
Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice.
Sex
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 SamplesWe wanted to determine how type II versus type III Toxoplasma infection affect host gene expression
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Cell line
View SamplesThe ectopic expression of a Col10a1-13del transgene in osteocytes induced ER stress, compromising their differentiation and expression of Sclerostin, resulting in generalized bone overgrowth resembling human crainodiaphyseal chondrodysplasia (CCD).
Activating the unfolded protein response in osteocytes causes hyperostosis consistent with craniodiaphyseal dysplasia.
Specimen part
View Samples