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

doi:10.1007/s13238-018-0517-8

Protein Cell

2018, Vol. 9

Issue (4) : 333-350 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 Wei⁶, Wei Li⁴, Jinghui Lei⁴, Yu Huang⁷, Yanmei Sang⁸, Piu Chan⁴, Chang Chen^2,³, Jing Jing^1,³(

), Keiichiro Suzuki^9,¹⁰(

), Juan Carlos Izpisua Belmonte¹¹(

), Guang-Hui Liu^2,^3,^4,¹²(

)

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

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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.

Keywords WRN lamin HGPS Werner syndrome stem cell aging

Corresponding Author(s): Zeming Wu,Weiqi Zhang,Moshi Song,Jing Jing,Keiichiro Suzuki,Juan Carlos Izpisua Belmonte,Guang-Hui Liu

Issue Date: 27 April 2018

Cite this article:

Zeming Wu,Weiqi Zhang,Moshi Song, et al. Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome[J]. Protein Cell, 2018, 9(4): 333-350.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-018-0517-8
https://academic.hep.com.cn/pac/EN/Y2018/V9/I4/333

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