Protein & Cell >

2018 , Vol. 9 >Issue 4: 333 - 350

DOI: https://doi.org/10.1007/s13238-018-0517-8

RESEARCH ARTICLE

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

  • Zeming Wu 1,2,3 ,
  • Weiqi Zhang 2,3,4 ,
  • Moshi Song 3,5 ,
  • Wei Wang 2,3 ,
  • Gang Wei 6 ,
  • Wei Li 4 ,
  • Jinghui Lei 4 ,
  • Yu Huang 7 ,
  • Yanmei Sang 8 ,
  • Piu Chan 4 ,
  • Chang Chen 2,3 ,
  • Jing Jing , 1,3 ,
  • Keiichiro Suzuki , 9,10 ,
  • Juan Carlos Izpisua Belmonte , 11 ,
  • Guang-Hui Liu , 2,3,4,12
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  • 1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 2. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • 3. University of Chinese Academy of Sciences, Beijing 100049, China
  • 4. National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
  • 5. State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 6. Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
  • 7. Department of Medical genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
  • 8. Department of Pediatric Endocrinology and Genetic Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
  • 9. Institute for Advanced Co-Creation Studies, Osaka University, Osaka 560-8531, Japan
  • 10. Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan
  • 11. Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla 92037, USA
  • 12. Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China

Received date: 18 Jan 2018

Accepted date: 08 Feb 2018

Published date: 27 Apr 2018

Copyright

2018 The Author(s) 2018. This article is an open access publication
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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) 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.

Key words： WRN; lamin; HGPS; Werner syndrome; stem cell; aging

Cite this article

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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