ArticleNature cell biology2017
ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors.
Erratum issuedOpen access · bronzeAbstract read
In one paragraph
Article in Nature cell biology, 2017. 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 26 papers.
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26citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Cellular senescence and aging: molecular mechanisms and convergent pathways.Cellular and molecular life sciences : CMLS · 2026Review
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- Genes as Genome Stabilizers in Pluripotent Stem Cells.Advances in experimental medicine and biology · 2025Review
- Gene Delivery via Octadecylamine-Based Nanoparticles for iPSC Generation from CCD1072-SK Fibroblast Cells.Current issues in molecular biology · 2024Article
- ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations.Brain : a journal of neurology · 2024Article
- Article
- Confinement plus myosin-II suppression maximizes heritable loss of chromosomes, as revealed by live-cell ChReporters.Journal of cell science · 2023Article
- Taiji-reprogram: a framework to uncover cell-type specific regulators and predict cellular reprogramming cocktails.NAR genomics and bioinformatics · 2021Article
- In Silico Analysis to Explore Lineage-Independent and -Dependent Transcriptional Programs Associated with the Process of Endothelial and Neural Differentiation of Human Induced Pluripotent Stem Cells.Journal of clinical medicine · 2021Article
- Reprogramming enriches for somatic cell clones with small-scale mutations in cancer-associated genes.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Review
- Acquisition of chromosome 1q duplication in parental and genome-edited human-induced pluripotent stem cell-derived neural stem cells results in their higher proliferation rate in vitro and in vivo.Cell proliferation · 2020Article
- Glis1 facilitates induction of pluripotency via an epigenome-metabolome-epigenome signalling cascade.Nature metabolism · 2020Article
- The SIRT6 activator MDL-800 improves genomic stability and pluripotency of old murine-derived iPS cells.Aging cell · 2020Article
- Retention of Somatic Memory Associated with Cell Identity, Age and Metabolism in Induced Pluripotent Stem (iPS) Cells Reprogramming.Stem cell reviews and reports · 2020Review
- An Insight into Reprogramming Barriers to iPSC Generation.Stem cell reviews and reports · 2020Review
- Reprogramming of Pluripotency-Specific microRNA Signatures Is Not Essential to Generate Inducible Pluripotent Stem Cells.Cellular reprogramming · 2020Article
- Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle.The Journal of cell biology · 2019Article
- Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease.Nature neuroscience · 2019Article
- Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development.Development (Cambridge, England) · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 7 institutions in 2 countries.
Maria SkamagkiCancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA.
Cristina CorreiaDepartment of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55904, USA.
Percy YeungDepartment of Obstetrics, Gynecology and Reproductive Sciences, Child Health Institute of New Jersey, New Brunswick, New Jersey 08901, USA.
Timour BaslanHoward Hughes Medical Institute, Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Samuel BeckDepartment of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
Cheng ZhangDepartment of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55904, USA.
Christian A RossDepartment of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55904, USA.
Lam DangCancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA.
Zhong LiuDepartment of Biochemistry and Molecular Genetics, Stem Cell Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Simona GiuntaLaboratory of Chromosome and Cell Biology, The Rockefeller University, New York, New York 10065, USA.
Tzu-Pei ChangCancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA.
Joye WangCancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA.
Aparna AnanthanarayananCancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA.
Martina BohndorfInstitute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, Düsseldorf D-40225, Germany.
Benedikt BosbachHoward Hughes Medical Institute, Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
James AdjayeInstitute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, Düsseldorf D-40225, Germany.
Hironori FunabikiLaboratory of Chromosome and Cell Biology, The Rockefeller University, New York, New York 10065, USA.ORCID http://orcid.org/0000-0003-4831-4087
Jonghwan KimDepartment of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.ORCID http://orcid.org/0000-0002-9919-9843
Scott LoweHoward Hughes Medical Institute, Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
James J CollinsDepartment of Biological Engineering, Massachusetts Institute of Technology, Broad Institute of MIT and Harvard, and Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02118, USA.
Chi-Wei LuDepartment of Obstetrics, Gynecology and Reproductive Sciences, Child Health Institute of New Jersey, New Brunswick, New Jersey 08901, USA.
Hu LiDepartment of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55904, USA.ORCID http://orcid.org/0000-0001-5957-5472
Rui ZhaoDepartment of Biochemistry and Molecular Genetics, Stem Cell Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.ORCID http://orcid.org/0000-0003-3769-6550
Kitai KimCancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA.ORCID http://orcid.org/0000-0001-9782-9429
Memorial Sloan Kettering Cancer Center · USMayo Clinic · USHeinrich Heine University Düsseldorf · DERockefeller University · USThe University of Texas at Austin · USUniversity of Alabama at Birmingham · USBroad Institute · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MScientific ReagentsP01CA087497 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI PRIVES, CAROL · 2000 to 2021
$35.4MCustomized stem cells for clinical application in blood disordersR24DK092760 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2011 to 2018
$10.7MInvestigating regulators controlling differentiation potential of ES cellsR01GM112722 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI KIM, JONGHWAN · 2015 to 2023
$2.8MA new hypothesis: role of p53 inhibitory factors in cellular reprogrammingR01AG043531 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI KIM, KITAI · 2014 to 2018
$2.3MA network platform to connect drug response and prognosis phenotypes for cancersR01CA196631 · NCI · MAYO CLINIC ROCHESTER · PI LI, HU · 2016 to 2018
$1.2MHematopoietic potential of histocompatible embryonic stem cell linesR00HL093212 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI KIM, KITAI · 2012 to 2014
$717kAlternative Cleavage and Polyadenylation in Trophoblast DifferentiationR21HD081682 · NICHD · RBHS-NEW JERSEY MEDICAL SCHOOL · PI LU, CHI-WEI, TIAN, BIN · 2015 to 2016
$435kNCI NIH HHS P01 CA087497NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA196631NHLBI NIH HHS R00 HL093212NIA NIH HHS R01 AG043531NICHD NIH HHS R21 HD081682NIDDK NIH HHS R24 DK092760NIGMS NIH HHS R01 GM112722
Abstract
Induced pluripotent stem cells (iPSCs), which are used to produce transplantable tissues, may particularly benefit older patients, who are more likely to suffer from degenerative diseases. However, iPSCs generated from aged donors (A-iPSCs) exhibit higher genomic instability, defects in apoptosis and a blunted DNA damage response compared with iPSCs generated from younger donors. We demonstrated that A-iPSCs exhibit excessive glutathione-mediated reactive oxygen species (ROS) scavenging activity, which blocks the DNA damage response and apoptosis and permits survival of cells with genomic instability. We found that the pluripotency factor ZSCAN10 is poorly expressed in A-iPSCs and addition of ZSCAN10 to the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) during A-iPSC reprogramming normalizes ROS-glutathione homeostasis and the DNA damage response, and recovers genomic stability. Correcting the genomic instability of A-iPSCs will ultimately enhance our ability to produce histocompatible functional tissues from older patients' own cells that are safe for transplantation.
Indexed as
Cellular ReprogrammingGenomic InstabilityTissue DonorsAdult Stem CellsAgedAge FactorsAgingAnimalsAnimals, NewbornApoptosisCell DifferentiationCell ProliferationCells, CulturedCellular Reprogramming TechniquesDNA-Binding ProteinsDNA DamageDNA-Binding ProteinsGlutathioneKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsMYC protein, humanOctamer Transcription Factor-3POU5F1 protein, humanProto-Oncogene Proteins c-mycReactive Oxygen SpeciesSOX2 protein, humanSOXB1 Transcription FactorsTranscription FactorsZSCAN10 protein, humanZscan10 protein, mouse
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