Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome

• DOI: 10.1007/s13238-018-0517-8
• Publication Date: 2018-02-23T14:45:55Z
• Authors: Zeming Wu; Weiqi Zhang; Moshi Song; Wei Wang; Gang Wei; Wei Li; Jinghui Lei; Yu Huang; Yanmei Sang; Piu Chan; Chang Chen; Jing Qu; Keiichiro Suzuki; Juan Carlos Izpis...; Guang-Hui Liu
• Keywords: Progeria; LMNA; Premature aging; Werner syndrome; Senescence

Hutchinson-Gilford progeria syndrome (HGPS) and Werner (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting production truncated protein product—progerin. WS mutations WRN encoding loss-of-function RecQ DNA helicase. Here, gene editing we created isogenic embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA biallelic knockout, for modeling pathogenesis, respectively. While ESCs endothelial (ECs) did not present any features premature senescence, HGPS- WS-mesenchymal (MSCs) showed aging-associated phenotypes different kinetics. WS-MSCs had early-onset mild aging while HGPS-MSCs exhibited late-onset acute characterisitcs. Taken together, our study compares contrasts distinct pathologies underpinning disorders, provides reliable stem-cell based models to identify new therapeutic strategies pathological physiological aging.