Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome
Protein & Cell
;
(12): 333-350, 2018.
Article
in English
| WPRIM
| ID: wpr-757991
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Physiology
/
Progeria
/
Werner Syndrome
/
Aging
/
Kinetics
/
DNA Helicases
/
Lamin Type A
/
Mesenchymal Stem Cells
/
Human Embryonic Stem Cells
/
Genetics
Limits:
Humans
Language:
English
Journal:
Protein & Cell
Year:
2018
Type:
Article
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