Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome
Received date: 18 Jan 2018
Accepted date: 08 Feb 2018
Published date: 27 Apr 2018
Copyright
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.
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 . Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome[J]. Protein & Cell, 2018 , 9(4) : 333 -350 . DOI: 10.1007/s13238-018-0517-8
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