{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang W"],"funding":["National Basic Research Program of China","Key Research Program of the Chinese Academy of Sciences","National High Technology Research and Development Program of China","Strategic Priority Research Program of the Chinese Academy of Sciences","NIA NIH HHS","NSFC","National Natural Science Foundation of China","China Postdoctoral Science Foundation","Thousand Young Talents program of China","Beijing Natural Science Foundation"],"pagination":["1160-3"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4494668"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["348(6239)"],"pubmed_abstract":["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"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging."],"pmcid":["PMC4494668"],"funding_grant_id":["2012CB966704","2015AA020307","5142016","81371342","81300261","SIMM1302KF-17","31201111","81300677","81471407","KJZDEW-TZ-L05","81471414","2015CB964800","F32 AG047770","31322037","81401159","XDA01020312","2013M530751","31222039","2014CB964600","7141005","81271266","81422017","2014CB910500","81330008"],"pubmed_authors":["Ocampo A","Shi L","Aizawa E","Qu J","Goebl A","Suzuki K","Tang F","Liu X","Wang P","Bai R","Guan D","Ding Z","Wang Y","Wang Z","Ren R","Zhou J","Yuan T","Yang J","Li J","Liu GH","Soligalla RD","Chen C","Belmonte JC","Li M","Yang F","Zhang W","Pan H","Li X","Li Y","Esteban CR","Duan S","Xu X","Yi F","Reddy P"],"additional_accession":[]},"is_claimable":false,"name":"Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.","description":"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","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jun","modification":"2026-04-30T14:06:26.613Z","creation":"2019-03-27T01:54:43Z"},"accession":"S-EPMC4494668","cross_references":{"pubmed":["25931448"],"doi":["10.1126/science.aaa1356"]}}