Comment[ArrayExpressAccession] E-GEOD-24487
Public Release Date 2011-03-14
Investigation Title Recapitulation of human premature aging by using iPSCs from Hutchinson-Gilford progeria syndrome
Comment[Submitted Name] Recapitulation of human premature aging by using iPSCs from Hutchinson-Gilford progeria syndrome
Experiment Description Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature aging disease1-5, characterized by premature atherosclerosis and degeneration of vascular smooth muscle cells (SMCs)6-8. HGPS is caused by a single-point mutation in the LMNA gene, resulting in the generation of progerin, a truncated mutant of lamin A. Accumulation of progerin leads to various aging-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin9-12. Here, we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS-iPSCs, progerin and its associated aging consequences are restored. In particular, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescent SMC phenotypes associated with vascular aging. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs) as a component of the progerin-containing protein complex. The absence of nuclear DNAPKcs correlates with premature as well as physiological aging. Since progerin also accumulates during physiological aging6,12,13, our results provide an in vitro iPSC-based model with an acceleration progerin accumulation to study the pathogenesis of human premature and physiological vascular aging. Microarray gene expression profiling was done to: (1) Compare differences between WT fibroblasts and fibroblasts from patients suffering of the Hutchinson-Gilford progeria syndrome (2) Check that iPSC originating from WT and patients are in fact similar to ESC
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Term Source Name EFO
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Term Source File http://www.ebi.ac.uk/efo/efo.owl
Person Last Name Boue Liu Barkho Ruiz Diep Yang Qu Kurian Walsh Panopoulos Thompson Boue Fung Zhang Yates III Izpisua-Belmonte
Person First Name Stephanie Guang-Hui Basam Sergio Dinh Sheng-Lian Jing Leo Christopher Athanasia James Stephanie Ho-Lim Kun John Juan-Carlos
Person Mid Initials D
Person Email geo@ncbi.nlm.nih.gov
Person Affiliation CMRB
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Person Address CMRB, Dr Aiguader 88, Barcelona, Spain
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Protocol Name P-GSE24487-1 P-GSE24487-5 P-GSE24487-2 P-GSE24487-9 P-GSE24487-7 P-GSE24487-6 P-GSE24487-8 P-GSE24487-3 P-GSE24487-4
Protocol Description ID_REF =
VALUE = RMA normalized autosome probes-only The GeneChip microarray processing was performed by the Functional Genomica Core in the Institute for Research in Biomedicine (Barcelona, Spain) according to the manufacturerM-bM-^@M-^Ys protocols (Affymetrix, Santa Clara, CA). The amplification and labeling were processed as indicated in Nugen protocol with 25ng starting RNA. For each sample, 3.75ug ssDNA were labeled and hybridized to the Affymetrix HG-U133 Plus 2.0 chips. All fibroblasts were cultured in 5% CO2 and at 37M-0C in DMEM containing 15% FBS, 2 mM L-glutamine, 0.1 mM non-essential aminoacids, sodium Pyruvate, and 55 M-NM-