ArticleScience (New York, N.Y.)2015
Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 344 papers.
0numbers the graph read from it
0cells of the map it votes in
344citing papers in PubMed
24.9field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
344 citing papers in PubMed, 536 citations in OpenAlex.
- Cryptic transcription in aging.iScience · 2026Review
- HMGA1-HP1β axis regulates premature aging in Hutchinson-Gilford progeria syndrome through chromatin remodeling.Nature communications · 2026Article
- The cardiac 4D nucleome: nuclear and chromatin dynamics across development, disease and ageing.Nature reviews. Cardiology · 2026Review
- The oocyte-enriched metabolite serotonin alleviates cellular senescence and aging phenotypes in the mouse.The EMBO journal · 2026Article
- Review
- HPL-2/HP1 and MET-2/SETDB1 bind distinct co-factors that promote heterochromatic foci, gene repression and organogenesis independently of H3K9 methylation.bioRxiv : the preprint server for biology · 2026Article
- Centenarian SIRT6 variants elevate SIRT6 protein and enhance cellular senescence resistance.Research square · 2026Article
- Local SNP-explained methylation variation reveals genetically anchored and exposure-associated methylation architecture in the human brain.bioRxiv : the preprint server for biology · 2026Article
- Review
- The entropic view of aging: from thermodynamics to biology.Life medicine · 2026Article
- Organoids: generation strategies, applications, and future challenges.Stem cell research & therapy · 2026Review
- Crosstalk between lipid metabolism and epigenetics in cellular senescence and age-related diseases.npj aging · 2026Review
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- Deficiency of Werner RecQ-type DNA helicase causes premature malnutrition in zebrafish.iScience · 2026Article
- BMI1 represses G-quadruplex DNA formation to maintain genomic stability during replication.The Journal of biological chemistry · 2026Article
- Neuroendocrine-associated epigenetic factors in cellular senescence: mechanisms and therapeutic implications.Biogerontology · 2026Review
- Loss of SETDB1-mediated H3K9me3 in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons.Nucleic acids research · 2026Article
- Lamin A/C-regulated cysteine catabolic flux modulates stem cell fate through epigenome reprogramming.Nature metabolism · 2026Article
- Novel Homozygous Variants in CIDEC and WRN in a Young Female with Lipodystrophy and Thyroid Cancer.International journal of molecular sciences · 2026Article
- From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging.Frontiers in aging · 2026Review
284 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
34 authors at 7 institutions in 2 countries.
Weiqi ZhangNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Jingyi LiBiodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
Keiichiro SuzukiGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jing QuState Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Ping WangNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Junzhi ZhouNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Xiaomeng LiuBiodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
Ruotong RenNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Xiuling XuNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Alejandro OcampoGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tingting YuanNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Jiping YangNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Ying LiNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Liang ShiDiagnosis and Treatment Center for Oral Disease, the 306th Hospital of the PLA, Beijing, China.
Dee GuanNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Huize PanNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Shunlei DuanNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Zhichao DingNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Mo LiGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Fei YiDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ruijun BaiState Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Yayu WangDiagnosis and Treatment Center for Oral Disease, the 306th Hospital of the PLA, Beijing, China.
Chang ChenNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Fuquan YangNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Xiaoyu LiCollege of Life Sciences, Peking University, Beijing 100871, China.
Zimei WangThe Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China.
Emi AizawaGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
April GoeblGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Universidad Católica San Antonio de Murcia, Campus de los Jerónimos s/n, 30107 Guadalupe, Murcia, Spain.
Rupa Devi SoligallaGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Pradeep ReddyGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Concepcion Rodriguez EstebanGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Fuchou TangBiodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.
Guang-Hui LiuNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Beijing Institute for Brain Disorders, Beijing 100069, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.
Juan Carlos Izpisua BelmonteGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.
Institute of Biophysics · CNSalk Institute for Biological Studies · USChinese Academy of Sciences · CNPeking University · CNInstitute of Zoology · CNMinistry of Education of the People's Republic of China · CNStanford University · US
Funding
Investigating the role of mitochondria in aging using a model of Werner SyndromeF32AG047770 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI OCAMPO, ALEJANDRO · 2014 to 2015
$109kNIA NIH HHS F32 AG047770
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 heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.
Indexed as
Cellular SenescenceAgingAnimalsCell DifferentiationCentromereChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsEpigenesis, GeneticExodeoxyribonucleasesGene Knockout TechniquesHEK293 CellsHeterochromatinHumansMembrane ProteinsMesenchymal Stem CellsCBX5 protein, humanChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsExodeoxyribonucleasesHeterochromatinlamina-associated polypeptide 2Membrane ProteinsMethyltransferasesRecQ HelicasesRepressor ProteinsSUV39H1 protein, humanWerner Syndrome HelicaseWRN protein, human
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.