ArrayExpress Uploader03825bj-fib_1: BJ (CRL-2522) fibroblasts were purchased from ATCC.ATCCbj-fib_2: BJ (CRL-2522) fibroblasts were purchased from ATCC.ATCChgps-fib_1: Human HGPS fibroblasts AG01972, AG11498, AG06297, and normal fibroblasts GM00038 (9 year), AG05247 (87 year), AG09602 (92 year) were purchased from Coriell Cell RepositoryCoriell Cell Repositories http://ccr.coriell.org/Sections/Search/Search.aspx?PgId=165&q=AG01972hgps-fib_2: Human HGPS fibroblasts AG01972, AG11498, AG06297, and normal fibroblasts GM00038 (9 year), AG05247 (87 year), AG09602 (92 year) were purchased from Coriell Cell RepositoryCoriell Cell Repositories http://ccr.coriell.org/Sections/Search/Search.aspx?PgId=165&q=AG01972bj-ipsc_1: BJ normal human fibroblasts (CRL-2522) were from ATCC and reprogrammed to iPSC with the protocol defined belowATCCbj-ipsc_2: BJ normal human fibroblasts (CRL-2522) were from ATCC and reprogrammed to iPSC with the protocol defined belowATCChgps-ipsc_1: Human HGPS fibroblasts AG01972, AG11498, AG06297, and normal fibroblasts GM00038 (9 year), AG05247 (87 year), AG09602 (92 year) were purchased from Coriell Cell Repository and reprogrammed using the protocol belowCoriell Cell Repositories http://ccr.coriell.org/Sections/Search/Search.aspx?PgId=165&q=AG01972hgps-ipsc_2: Human HGPS fibroblasts AG01972, AG11498, AG06297, and normal fibroblasts GM00038 (9 year), AG05247 (87 year), AG09602 (92 year) were purchased from Coriell Cell Repository and reprogrammed using the protocol below.Coriell Cell Repositories http://ccr.coriell.org/Sections/Search/Search.aspx?PgId=165&q=AG01972h9-esc_1: H9 hESCs (WiCell Research)WiCell Researchh9-esc_2: H9 hESCs (WiCell Research)WiCell Researcharrayexpress_sid4Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature aging disease1-5, characterized by premature...21346760E-GEOD-24487/profile/8773/arrayexpressuploader210atherosclerosishutchinson-gilford progeria syndromelamin amusclenuclear laminapointproteinprotein complexsyndromeDec.12, 2014Falserecapitulation-of-human-premature-aging-by-using-iE-GEOD-24487_A-AFFY-44Recapitulation of human premature aging by using iPSCs from Hutchinson-Gilford progeria syndromeSep.15, 2014Hutchinson-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 ESChttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-24487humanhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-24487/samples/