ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors

Maria Skamagki; Cristina Correia; Percy Yeung; Timour Baslan; Samuel Beck; Cheng Zhang; Christian A. Ross; Lam Dang; Zhong Liu; Simona Giunta; Tzu Pei Chang; Joye Wang; Aparna Ananthanarayanan; Martina Bohndorf; Benedikt Bosbach; James Adjaye; Hironori Funabiki; Jonghwan Kim; Scott Lowe; James J. Collins; Chi Wei Lu; Hu Li; Rui Zhao; Kitai Kim

doi:10.1038/ncb3598

ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors

Maria Skamagki, Cristina Correia, Percy Yeung, Timour Baslan, Samuel Beck, Cheng Zhang, Christian A. Ross, Lam Dang, Zhong Liu, Simona Giunta, Tzu Pei Chang, Joye Wang, Aparna Ananthanarayanan, Martina Bohndorf, Benedikt Bosbach, James Adjaye, Hironori Funabiki, Jonghwan Kim, Scott Lowe, James J. CollinsChi Wei Lu, Hu Li, Rui Zhao, Kitai Kim

Pharmacology

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1037-1048
Number of pages	12
Journal	Nature Cell Biology
Volume	19
Issue number	9
DOIs	https://doi.org/10.1038/ncb3598
State	Published - Sep 1 2017

ASJC Scopus subject areas

Cell Biology

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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., ... Kim, K. (2017). ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors. Nature Cell Biology, 19(9), 1037-1048. https://doi.org/10.1038/ncb3598

Skamagki, M, Correia, C, Yeung, P, Baslan, T, Beck, S, Zhang, C, Ross, CA, Dang, L, Liu, Z, Giunta, S, Chang, TP, Wang, J, Ananthanarayanan, A, Bohndorf, M, Bosbach, B, Adjaye, J, Funabiki, H, Kim, J, Lowe, S, Collins, JJ, Lu, CW, Li, H, Zhao, R & Kim, K 2017, 'ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors', Nature Cell Biology, vol. 19, no. 9, pp. 1037-1048. https://doi.org/10.1038/ncb3598

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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.",

author = "Maria Skamagki and Cristina Correia and Percy Yeung and Timour Baslan and Samuel Beck and Cheng Zhang and Ross, {Christian A.} and Lam Dang and Zhong Liu and Simona Giunta and Chang, {Tzu Pei} and Joye Wang and Aparna Ananthanarayanan and Martina Bohndorf and Benedikt Bosbach and James Adjaye and Hironori Funabiki and Jonghwan Kim and Scott Lowe and Collins, {James J.} and Lu, {Chi Wei} and Hu Li and Rui Zhao and Kitai Kim",

note = "Funding Information: K.K. is supported by the NIH (R00HL093212), NIH (R01AG043531), TriStem-Star Foundation (2013-049), Louis V. Gerstner, Jr. Young Investigators awards, Geoffrey Beene Junior Chair Award, Sidney Kimmel Scholar Award, Alfred W. Bressler Scholars Endowment Fund and MSKCC Society Fund. MSKCC Core Facilities are supported by NIH Cancer Center support grant P30 CA008748. R.Z. is supported by the UAB Development Fund. H.L. is supported by the NIH (CA196631-01A1) and Mayo Clinic Center for Individualized Medicine. C.-W.L. is supported by the NIH (R21HD081682). J.J.C. is supported by the HHMI and NIH (R24DK092760). S.L. is supported by the HHMI and NIH (P01CA087497). J.K. is supported by the NIH (R01GM112722). H.F. is supported by the TriStem-Star Foundation (2013-049). J.A. acknowledges support from the medical faculty of Heinrich Heine University, D{\"u}sseldorf. T.B. is supported by the MSKCC Single Cell Sequencing Initiative, William and Joyce O{\textquoteright}Neil Research Fund and STARR visiting fellows programme. S.G. is supported by the American Italian Cancer Foundation and a Women in Science Rockefeller fellowship. Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature.",

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doi = "10.1038/ncb3598",

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AU - Skamagki, Maria

AU - Correia, Cristina

AU - Yeung, Percy

AU - Baslan, Timour

AU - Beck, Samuel

AU - Zhang, Cheng

AU - Ross, Christian A.

AU - Dang, Lam

AU - Liu, Zhong

AU - Giunta, Simona

AU - Chang, Tzu Pei

AU - Wang, Joye

AU - Ananthanarayanan, Aparna

AU - Bohndorf, Martina

AU - Bosbach, Benedikt

AU - Adjaye, James

AU - Funabiki, Hironori

AU - Kim, Jonghwan

AU - Lowe, Scott

AU - Collins, James J.

AU - Lu, Chi Wei

AU - Li, Hu

AU - Zhao, Rui

AU - Kim, Kitai

N1 - Funding Information: K.K. is supported by the NIH (R00HL093212), NIH (R01AG043531), TriStem-Star Foundation (2013-049), Louis V. Gerstner, Jr. Young Investigators awards, Geoffrey Beene Junior Chair Award, Sidney Kimmel Scholar Award, Alfred W. Bressler Scholars Endowment Fund and MSKCC Society Fund. MSKCC Core Facilities are supported by NIH Cancer Center support grant P30 CA008748. R.Z. is supported by the UAB Development Fund. H.L. is supported by the NIH (CA196631-01A1) and Mayo Clinic Center for Individualized Medicine. C.-W.L. is supported by the NIH (R21HD081682). J.J.C. is supported by the HHMI and NIH (R24DK092760). S.L. is supported by the HHMI and NIH (P01CA087497). J.K. is supported by the NIH (R01GM112722). H.F. is supported by the TriStem-Star Foundation (2013-049). J.A. acknowledges support from the medical faculty of Heinrich Heine University, Düsseldorf. T.B. is supported by the MSKCC Single Cell Sequencing Initiative, William and Joyce O’Neil Research Fund and STARR visiting fellows programme. S.G. is supported by the American Italian Cancer Foundation and a Women in Science Rockefeller fellowship. Publisher Copyright: © 2017 Macmillan Publishers Limited, part of Springer Nature.

PY - 2017/9/1

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N2 - 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.

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ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors

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