%A Zeming Wu, Weiqi Zhang, Moshi Song, Wei Wang, Gang Wei, Wei Li, Jinghui Lei, Yu Huang, Yanmei Sang, Piu Chan, Chang Chen, Jing Jing, Keiichiro Suzuki, Juan Carlos Izpisua Belmonte, Guang-Hui Liu %T Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome %0 Journal Article %D 2018 %J Protein Cell %J Protein & Cell %@ 1674-800X %R 10.1007/s13238-018-0517-8 %P 333-350 %V 9 %N 4 %U {https://journal.hep.com.cn/pac/EN/10.1007/s13238-018-0517-8 %8 2018-04-27 %X

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) LMNAmutation 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.