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

Protein & Cell
Zeming WuGuang-Hui Liu

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) LMNA mutation 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.

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Citations

Apr 3, 2019·Protein & Cell·Xiaojuan HeUNKNOWN Major Program Expert Group
Aug 3, 2018·Protein & Cell·Lingling GengGuang-Hui Liu
Jul 4, 2019·Cells·Raquel Romero-BuenoAgnieszka Dobrzynska
Oct 26, 2018·Circulation Research·Weiqi ZhangGuang-Hui Liu
Dec 29, 2019·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Motoko Niida-KawaguchiNoriyuki Shibata
Feb 6, 2020·Nature Reviews. Molecular Cell Biology·Weiqi ZhangJuan Carlos Izpisua Belmonte
May 20, 2020·Nucleic Acids Research·Huifang HuJing Qu
Jul 22, 2019·Human Genetics·Taylor McNeelyIsabel Beerman
Jul 28, 2019·Nature Communications·Liping DengGuang-Hui Liu
Jul 31, 2020·Protein & Cell·Pradeep ReddyJuan Carlos Izpisua Belmonte
Aug 28, 2020·Cells·Alice-Anaïs VarletCatherine Badens
Oct 10, 2020·Nucleic Acids Research·Zeming WuJing Qu
Jan 8, 2021·Science Translational Medicine·Wei WangGuang-Hui Liu
Mar 12, 2021·Nucleic Acids Research·Zhiqing DiaoJing Qu
Oct 23, 2020·Endocrine Journal·Huan LiHanqing Cai
Jan 14, 2022·Protein & Cell·Wei LiWeiqi Zhang

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Methods Mentioned

BETA
FACS
Knockout
PCR
Flow
Assay
fluorescence-activated cell sorting

Software Mentioned

Image J
Image Lab

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