Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

Détails

ID Serval
serval:BIB_7E1288D26ABF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.
Périodique
Science
Auteur(s)
Zhang W., Li J., Suzuki K., Qu J., Wang P., Zhou J., Liu X., Ren R., Xu X., Ocampo A., Yuan T., Yang J., Li Y., Shi L., Guan D., Pan H., Duan S., Ding Z., Li M., Yi F., Bai R., Wang Y., Chen C., Yang F., Li X., Wang Z., Aizawa E., Goebl A., Soligalla R.D., Reddy P., Esteban C.R., Tang F., Liu G.H., Belmonte J.C.
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Statut éditorial
Publié
Date de publication
05/06/2015
Peer-reviewed
Oui
Volume
348
Numéro
6239
Pages
1160-1163
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.
Mots-clé
Aging/genetics, Aging/metabolism, Animals, Cell Differentiation, Cellular Senescence, Centromere/metabolism, Chromosomal Proteins, Non-Histone/metabolism, DNA-Binding Proteins/metabolism, Epigenesis, Genetic, Exodeoxyribonucleases/genetics, Exodeoxyribonucleases/metabolism, Gene Knockout Techniques, HEK293 Cells, Heterochromatin/chemistry, Heterochromatin/metabolism, Humans, Membrane Proteins/metabolism, Mesenchymal Stromal Cells/metabolism, Methyltransferases/genetics, Methyltransferases/metabolism, Mice, Models, Biological, RecQ Helicases/genetics, RecQ Helicases/metabolism, Repressor Proteins/genetics, Repressor Proteins/metabolism, Werner Syndrome/genetics, Werner Syndrome/metabolism, Werner Syndrome Helicase
Pubmed
Web of science
Création de la notice
14/08/2018 9:34
Dernière modification de la notice
20/08/2019 14:39
Données d'usage