ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors
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Author(s)
Skamagki, Maria
Correia, Cristina
Yeung, Percy
Baslan, Timour
Beck, Samuel
Zhang, Cheng
Ross, Christian A.
Dang, Lam
Liu, Zhong
Giunta, Simona
Date Issued
August 2017
Journal
Nature Cell Biology
Publisher
Nature Publishing Group
Citation
Skamagki, Maria et al. “ZSCAN10 Expression Corrects the Genomic Instability of iPSCs from Aged Donors.” Nature Cell Biology 19, 9 (August 2017): 1037–1048 © 2017 Macmillan Publishers Limited, part of Springer Nature
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/NCB3598
