Female human ESC-lines can carry active X-chromosomes (Xa) or an XIST-RNA-coated inactive X-chromosome (XiXIST+). Additionally, many ESC lines have abnormal X-chromosomeinactivation (XCI)-states where the Xi no longer expresses XIST-RNA and has transcriptionally active regions (eroded Xi=Xe). The fate of each XCI-state upon differentiation is unclear because individual lines often contain a mixture of XCI-states. Here, we established homogeneous XiXa, XeXa, and XaXa ESC-lines. Employing RNA-FISH, RNA-sequencing and DNA methylation analyses, we found that these lines were unable to initiate XIST-expression and X-chromosome-wide silencing upon differentiation indicating that the ESC XCI-state is maintained in differentiated cells. Consequently, differentiated XeXa and XaXa cells displayed higher levels of X-linked gene-expression than XiXa cells. Although global transcriptional compensation between X-chromosomes and autosomes is not required for female ESC-differentiation, the degree of X-chromosome-silencing influences differentiation efficiencies. Our data suggest that the XiXIST+Xa state is inherent to human ESCs and that all other XCI-states, including XaXa, are abnormal and arise during ESC-derivation or maintenance. Overall design: RNA-seq was used to measure the expression state of X-linked and autosomal genes in undifferentiated human embryonic stem cells with different X-chromosome states and their differentiated cells.
Human Embryonic Stem Cells Do Not Change Their X Inactivation Status during Differentiation.
Specimen part, Subject
View SamplesRhoBTB2 is a novel Rho GTPase that undergoes loss, underexpression and mutation in breast and lung cancer. We have shown that we can mimic loss of RhoBTB2 through siRNA treatment of primary cells. We propose to perform comparative microarray analysis of primary lung cells to establish the identification of the gene targets of RhoBTb2 regulation.
The atypical Rho GTPase RhoBTB2 is required for expression of the chemokine CXCL14 in normal and cancerous epithelial cells.
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View SamplesHeterotopic cardiac transplants were constructed in male Wistar Furth (allograft donor) and ACI (host) rats. Rats were divided into three groups consisting of no treatment, treatment with a sub-therapeutic dose of cyclosporin A, and treated with combination of a sub-therapeutic dose of cyclosporin A and allochimeric peptide. The allografts were harvested at defined periods post-transplantation and RNA was harvested to monitor gene expression changes resulting from the various treatments in T-cells and in heart cells.
Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.
Sex, Specimen part
View SamplesA number of breast or colon specific genes predictive of the relapse status were used in comparing the outcome from matched fresh frozen and stored in RNAlater preservative.
Prognostic gene expression signatures can be measured in tissues collected in RNAlater preservative.
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Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.
Sex, Age, Specimen part, Subject
View SamplesWith a focus on rheumatoid arthritis (RA), we sought new insight into genetic mechanisms of adaptive immune dysregulation to help prioritise molecular pathways for targeting in this and related immune pathologies. Whole genome methylation and transcriptional data from isolated CD4+ T cells and B cells of >100 genotyped and phenotyped inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments, were obtained. Analysis integrated these comprehensive data with GWAS findings across IMDs and other publically available resources.
Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.
Sex, Age, Specimen part, Subject
View SamplesWith a focus on rheumatoid arthritis (RA), we sought new insight into genetic mechanisms of adaptive immune dysregulation to help prioritise molecular pathways for targeting in this and related immune pathologies. Whole genome methylation and transcriptional data from isolated CD4+ T cells and B cells of >100 genotyped and phenotyped inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments, were obtained. Analysis integrated these comprehensive data with GWAS findings across IMDs and other publically available resources.
Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.
Sex, Age, Specimen part, Subject
View Samples242 patients recruited from an early arthritis clinic donated RNA and DNA from freshly isolated and purified peripheral blood CD19+ B cells. Global gene expression measurement was carried out using Illumina BeadChip HT12v4 microarrays. Objectives included the identification of B cell transcripts differentially expressed between disease phenotypes, where all patients were naive to immunomodulatory therapy. In addition an eQTL analysis was carried out with reference to known genotype data for this cohort of patients
CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis: Implications for Causal Gene Identification.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells.
Specimen part, Cell line
View SamplesThe resultant heat map demonstrates the maturation of CD13+/ROR2+ cells as they proceed through cardiac differentiation. Overall design: RNA-seq analysis was preformed on RNA samples from undifferentiated hESCs, 13R2+ and 13R2- populations from day 3, 13R2+/NKX2-5+ and 13R2+/NKX2-5- from day 7, and 13R2+/NKX2-5+/a-MHC+ and 13R2+/NKX2-5+/MHC- from day 14
CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells.
No sample metadata fields
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