Project description:This SuperSeries is composed of the following subset Series: GSE41751: Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (expression) GSE41757: Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (ChIP-seq) GSE41763: Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (Hi-C) Refer to individual Series
Project description:Exon usage analysis in in vitro cultured fibroblast cells. To assay the genome-wide splicing changes during cellular senescence, we performed splicing analysis on young and old normal fibroblasts, and in fibroblasts +/- tert (telomerase protein subunit Tert immortalized). We analyzed primary fibroblasts from 5 healthy subjects at various passages and from 2 Hutchinson-Gilford Progeria Syndrome (HGPS) patients using the Affymetrix Human Exon 1.0 ST platform. Two or three technical replicates were performed.
Project description:Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin accumulation. However, the mechanism of how progerin causes cell defects is unclear in HGPS cells. To further investigate the possible mechanism, we used Flag-tagged progerin as bait in mass spectrometry to survey the possible regulatory factors.
Project description:we describe the utility of this novel platform in the field of genome medicine using a full-length approach to evaluate the relationship between transcriptional and mutational heterogeneity on single cells in dermal fibroblasts derived from patients with Hutchinson-Gilford progeria syndrome (HGPS)
Project description:we describe the utility of this novel platform in the field of genome medicine using a full-length approach to evaluate the relationship between transcriptional and mutational heterogeneity on single cells in dermal fibroblasts derived from patients with Hutchinson-Gilford progeria syndrome (HGPS)
Project description:we describe the utility of this novel platform in the field of genome medicine using a full-length approach to evaluate the relationship between transcriptional and mutational heterogeneity on single cells in dermal fibroblasts derived from patients with Hutchinson-Gilford progeria syndrome (HGPS)
Project description:The premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A1. Progerin is also sporadically expressed in wild type cells and has been linked to physiological aging. HGPS cells exhibit extensive nuclear defects including abnormal chromatin structure and increased DNA damage. At the organismal level, HGPS affects several tissues particularly of mesenchymal origin. How the cellular defects of HGPS cells lead to the organismal defects has been unclear. To begin to unravel how progerin leads to disease phenotypes, we analyzed time-dependent changes in transcriptional profiles in response to progerin expression in a hTERT-immortalized skin fibroblast cell line expressing either GFP-progerin or the GFP-wt lamin A control Keywords: time course, cell line comparison
Project description:To model Hutchinson-Gilford Progeria syndrome (HGPS), we differentiated patient-derived induced pluripotent stem cells (iPSCs) to vascular smooth muscle cells (VSMCs). We then performed gene expression profiling analysis using data obtained from RNA-seq of the serially passaged cells at passage7 and passage 14.
Project description:Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disease with widespread phenotypic features resembling premature aging. HGPS was recently shown to be caused by dominant mutations in the LMNA gene, resulting in the in-frame deletion of 50 amino acids near the carboxyl terminus of the encoded lamin A protein. Children with this disease typically succumb to myocardial infarction or stroke caused by severe atherosclerosis at an average age of 13 years. To elucidate further the molecular pathogenesis of this disease, we compared the gene expression patterns of three HGPS fibroblast cell lines heterozygous for the LMNA mutation with three normal, age-matched cell lines. We defined a set of 361 genes (1.1% of the approximately 33 000 genes analyzed) that showed at least a 2-fold, statistically significant change. The most prominent categories encode transcription factors and extracellular matrix proteins, many of which are known to function in the tissues severely affected in HGPS. The most affected gene, MEOX2/GAX, is a homeobox transcription factor implicated as a negative regulator of mesodermal tissue proliferation. Thus, at the gene expression level, HGPS shows the hallmarks of a developmental disorder affecting mesodermal and mesenchymal cell lineages. The identification of a large number of genes implicated in atherosclerosis is especially valuable, because it provides clues to pathological processes that can now be investigated in HGPS patients or animal models. Keywords: microarrays, Hutchinson–Gilford progeria syndrome, HGPS
Project description:Analysis of p53-deficient (E6-expressing) human vascular smooth muscle cells (VSMCs) that express progerin, a mutated form of lamin A resposible for Hutchinson- Gilford progeria syndrome (HGPS). p53 pathway is associated with HGPS. Results provide insight into molecular mechanisms underlying vascular dysfunction of HGPS caused by other than p53 pathway.
