ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors Journal Article

Authors: Skamagki, M.; Correia, C.; Yeung, P.; Baslan, T.; Beck, S.; Zhang, C.; Ross, C. A.; Dang, L.; Liu, Z.; Giunta, S.; Chang, T. P.; Wang, J.; Ananthanarayanan, A.; Bohndorf, M.; Bosbach, B.; Adjaye, J.; Funabiki, H.; Kim, J.; Lowe, S.; Collins, J. J.; Lu, C. W.; Li, H.; Zhao, R.; Kim, K.
Article Title: ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors
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.
Keywords: stress; glutathione; differentiation; mutations; gene-expression; dna-damage; oxidative; human fibroblasts; pluripotent stem-cells; human es cells; cancer
Journal Title: Nature Cell Biology
Volume: 19
Issue: 9
ISSN: 1465-7392
Publisher: Nature Publishing Group  
Date Published: 2017-09-01
Start Page: 1037
End Page: 1048
Language: English
ACCESSION: WOS:000408675600009
DOI: 10.1038/ncb3598
PUBMED: 28846095
PMCID: PMC5843481
Notes: Correction issued, see DOI: 10.1038/s41556-018-0269-y -- Article -- Source: Wos
Citation Impact
MSK Authors
  1. Scott W Lowe
    234 Lowe
  2. Kitai Kim
    13 Kim
  3. Benedikt Bosbach
    10 Bosbach
  4. Timour Baslan
    43 Baslan
  5. Lam Hoang Dang
    2 Dang
  6. Tzu-Pei Chang
    1 Chang
  7. Joye Wang
    1 Wang