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| Status |
Public on Mar 14, 2011 |
| Title |
Recapitulation of human premature aging by using iPSCs from Hutchinson-Gilford progeria syndrome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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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| Contributor(s) |
Liu G, Barkho B, Ruiz S, Diep D, Yang S, Qu J, Kurian L, Walsh C, Panopoulos AD, Thompson J, Boue S, Fung H, Zhang K, Yates III J, Izpisua-Belmonte J |
| Citation(s) |
21346760 |
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| Submission date |
Oct 01, 2010 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Stephanie Boue |
| Organization name |
CMRB
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| Street address |
Dr Aiguader 88
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| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA132521 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24487_RAW.tar |
50.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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