We have previously identified a prognostic 31-gene expression signature in locally advanced cervical cancer that is associated with tumor hypoxia and reflected by the dynamic contrast enhanced magnetic resonance (DCE-MR) image parameter ABrix. To bring the signature closer to clinical use, we here aimed to construct a classifier with key signature genes that retained an association to ABrix and separated the patients into groups with different hypoxia status and chemoradiotherapy outcome.
Integrative Analysis of DCE-MRI and Gene Expression Profiles in Construction of a Gene Classifier for Assessment of Hypoxia-Related Risk of Chemoradiotherapy Failure in Cervical Cancer.
Specimen part, Cell lineView Samples
Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion between pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem and progenitor cells (HSPCs), and mature hematopoietic cells. Quantification of chromatin composition by high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSPCs, with a further reduction in euchromatin as HSPCs transition into mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9a resulted in delayed hematopoietic stem cell (HSC) differentiation. Our results demonstrate significant global rearrangements of chromatin structure during embryonic and adult stem cell differentiation, and that heterochromatin formation by H3K9 methylation is an important regulator of HSC differentiation. Overall design: Examination of gene expression profile of in vitro cultured mouse HSC with the G9a inhibitor UNC0638
Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells.
Specimen part, Cell line, Treatment, SubjectView Samples
To understand at the molecular level the differences between old HSCs and young HSCs we have performed genome-wide analyses using Affymetrix Gene ST 1.0 microarrays with FACS purified cell populations. In contrast to other datasets comparing young and old HSCs, we compared both young and old HSCs and GMPs, and subtracted for genes that were also differentially expressed between young and old GMPs using a zero-intercept linear model. This allowed us to identify 913 significantly differentially expressed genes that were specific to old HSCs and segregated into different clusters.
Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells.
Here we are using RNA-Seq to study the effect of PRR14L knockdown on transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage. Overall design: RNAseq was performed on individual CFU-GM with shRNA-mediated PRR14L knockdown and scramble control to study the effects of PRR14L knockdown on the transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage.
PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.
Specimen part, SubjectView Samples
To explore the degree to which the glioma cell lines remained transcriptionally stable under diverse experimental conditions, we transplanted three different lines (U3020MG, U3047MG and U3065MG) intracranially to NOD-SCID mice; explanted the resulting tumors and cultured the cells for two passages, and then isolated RNA from the cell line prior to transplantation (U3020MG-p10, U3047MG-p7, U3065MG-p10), from the xenograft tumor and from the explanted cells.
The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived brain transcriptome profiling (RNA-seq) in neuropathic region specific Gaucher mouse brain compared with WT and Isofagamine treated mice of the same age and background and secondly to identify the DEmiRNA associated with the DEmRNA before and after treatment This will give us some insights to see if miRNA is also involved in the the regulation of the expression of the genes involved in the disease process before and after treatment. Methods: 42-45 days old 4L;C*, wild-type (WT) and Isofagamine treated 4L;C* mouse brain were generated by deep sequencing, in triplicate, using IlluminaHiseq. The sequence reads that passed quality filters were analyzed at the gene level with two methods: Burrows–Wheeler Aligner (BWA) followed and TopHat followed by DESeq. qRT–PCR validation was performed using TaqMan and SYBR Green assays Overall design: Regional brain mRNA profiles of ~42 -days old wild type (WT) and 4L;C* an d Isofagamine treated mice were generated by deep sequencing, in triplicate, using IlluminaHi Seq.
Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.
No sample metadata fieldsView Samples
Analysis of histone acetyl transferases (HATs) from the MYST and GNAT families in S. pombe to identify functional differences or overlap with regard to gene expression. Mutations were made to Elp3 and Gcn5 (GNAT family), and to Mst2 (MYST family). Mutants showed distinct phenotypes which were repressed or enhanced by mutant combinations.
Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation.
Cell line, TreatmentView Samples
Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C).
Cyclodextrin protects podocytes in diabetic kidney disease.
Cell lineView Samples