This SuperSeries is composed of the SubSeries listed below.
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
Specimen part, Cell line, Treatment
View SamplesSOX2 is an oncogene and a core pluripotency transcription factor. SOX2 has multiple roles in various malignancies, in the maintainance of pluripotency and during various stages of embryonic development. Human embryonal carcinoma cells express SOX2 and the loss of this results in their differentiation.
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
Specimen part, Cell line, Treatment
View SamplesAnalysis of mouse placenta retrieved at day 18.5pc from vitamin D (1,25-dihydroxyvitamin D3) receptor (Vdr) knockout, heterozygous and wild-type mice. Results provide insight into the molecular mechanisms underlying the effect of vitamin D on placental function.
Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome.
Specimen part
View SamplesRNA-directed DNA methylation (RdDM) is a transcriptional silencing mechanism mediated by small and long noncoding RNAs produced by the plant-specific RNA polymerases Pol IV and Pol V, respectively. Through a chemical genetics screen with a luciferase-based DNA methylation reporter, LUCL, we found that camptothecin, a compound with anti-cancer properties that targets DNA topoisomerase 1a (TOP1a) was able to de-repress LUCL by reducing its DNA methylation and H3K9 dimethylation (H3K9me2) levels. Further studies with Arabidopsis top1a mutants showed that TOP1a promotes RdDM by facilitating the production of Pol V-dependent long non-coding RNAs, AGONAUTE4 recruitment and H3K9me2 deposition at transposable elements (TEs). Overall design: 5 small RNA libraries were sequenced
DNA topoisomerase 1α promotes transcriptional silencing of transposable elements through DNA methylation and histone lysine 9 dimethylation in Arabidopsis.
Specimen part, Subject
View SamplesA zebrafish forward genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in the lysosomal hydrolase Cathepsin L that manifests the hallmarks of human lysosomal storage diseases. In uninfected mutants, macrophages progressively accumulate undigested material in their lysosomes, leading to impaired migration and the accumulation of unengulfed cell debris. During mycobacterial infection, these vacuolated macrophages cannot migrate to phagocytose infected macrophages undergoing apoptosis in the tuberculous granuloma. Consequently, unengulfed apoptotic macrophages undergo secondary necrosis causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal accumulations similarly impair migration to newly infecting mycobacteria. We find that important aspects of this phenotype are recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of alveolar macrophages from smokers exhibit lysosomal accumulations and do not migrate to Mycobacterium tuberculosis. This incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis. Overall design: A forward genetic screen for zebrafish larvae that are hypersusceptible to Mycobacterium marinum infection identified a mutation in the transcription factor snapc1b at 13: 37996163 (T->C). Individuals of wild type (T/T) and mutant (C/C) were genotyped and pooled respectively for RNA isolation and transcriptome analysis.
Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.
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View SamplesWe report the mRNA profile of aged mice (24 months old) fed either a control diet or a diet containing Rapamycin (14 ppm) for 3 months. After drug treatement, the hearts of the mice were removed and total mRNA was removed from the tissue. Analysis revealed that there were 700 significantly differentially expressed genes between the control fed group and the Rapamycin diet group by our analysis. Overall design: Heart tissue samples from age-matched control mice (n=10) and rapamycin fed mice (n=10) were extracted for total RNA. The samples were sequenced using Illumina HiSeq 2000 (50 basepair paired-end sequencing). The sequencing yielded quality scores greater than 30 with an average of 10 million reads per sample. 34,293 genes were mapped back to the MGSCv37 C57BL/6J mouse genome (maximum paired distance=300 and minimum=130, minimum number of reads per mapping = 5, maximum number of mismatches= 2, with the reads being mapped to unique sites in the genome).
Late-life rapamycin treatment reverses age-related heart dysfunction.
Age, Specimen part, Treatment, Subject
View SamplesZinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to determine how zinc is important to placental morphogenesis.
Zinc is a critical regulator of placental morphogenesis and maternal hemodynamics during pregnancy in mice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part, Subject
View SamplesEpigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part
View SamplesMutations in GRIN2B are associated with intellectual disability in humans. We generated iPSC derived mature cortical neurons with mutations in GRIN2B and compared them to isogenic control cells. We found that both loss of function (LOF) and reduced dosage (RD) mutations in GRIN2B lead to reduced expression of NMDAR genes and increased expression of marker of immaturity, including KI67 and MET. Overall design: Examination of transcriptome in iPSC-derved mature neurons with and without the presence of mutations in GRIN2B
Disruption of GRIN2B Impairs Differentiation in Human Neurons.
Subject
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