- Author:
Zeming WU
1
;
Weiqi ZHANG
2
;
Moshi SONG
3
;
Wei WANG
2
;
Gang WEI
4
;
Wei LI
5
;
Jinghui LEI
5
;
Yu HUANG
6
;
Yanmei SANG
7
;
Piu CHAN
5
;
Chang CHEN
2
;
Jing QU
8
;
Keiichiro SUZUKI
9
;
Juan Carlos Izpisua BELMONTE
10
;
Guang-Hui LIU
11
Author Information
- Publication Type:Journal Article
- Keywords: HGPS; WRN; Werner syndrome; aging; lamin; stem cell
- MeSH: Aging; genetics; physiology; DNA Helicases; genetics; Human Embryonic Stem Cells; metabolism; physiology; Humans; Kinetics; Lamin Type A; genetics; Mesenchymal Stem Cells; metabolism; physiology; Mutation; Progeria; genetics; physiopathology; Werner Syndrome; genetics; physiopathology
- From: Protein & Cell 2018;9(4):333-350
- CountryChina
- Language:English
- Abstract: Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product-progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Here, by gene editing we created isogenic human embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA mutation and biallelic WRN knockout, for modeling HGPS and WS pathogenesis, respectively. While ESCs and endothelial cells (ECs) did not present any features of premature senescence, HGPS- and WS-mesenchymal stem cells (MSCs) showed aging-associated phenotypes with different kinetics. WS-MSCs had early-onset mild premature aging phenotypes while HGPS-MSCs exhibited late-onset acute premature aging characterisitcs. Taken together, our study compares and contrasts the distinct pathologies underpinning the two premature aging disorders, and provides reliable stem-cell based models to identify new therapeutic strategies for pathological and physiological aging.