Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2019; 11(10): 729-747
Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.729
Genomic integrity of human induced pluripotent stem cells: Reprogramming, differentiation and applications
Clara Steichen, Zara Hannoun, Eléanor Luce, Thierry Hauet, Anne Dubart-Kupperschmitt
Clara Steichen, Thierry Hauet, INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers F-86021, France
Clara Steichen, Thierry Hauet, Université de Poitiers, Faculté de Médecine et Pharmacie, Bâtiment D1, 6 rue de la milétrie, TSA 51115, 86073 Poitiers Cedex 9, France
Zara Hannoun, Eléanor Luce, Anne Dubart-Kupperschmitt, INSERM U1193, Hôpital Paul Brousse, Villejuif F-94800, France
Zara Hannoun, Eléanor Luce, Anne Dubart-Kupperschmitt, UMR_S1193, Université Paris-Saclay, Hôpital Paul Brousse, Villejuif F-94800, France
Zara Hannoun, The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom
Eléanor Luce, Anne Dubart-Kupperschmitt, Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, Villejuif F-94807, France
Thierry Hauet, Service de Biochimie, Pôle Biospharm, CHU de Poitiers, Poitiers F-86021, France
Thierry Hauet, Fédération Hospitalo-Universitaire SUPORT, CHU de Poitiers, Poitiers F-86021, France
Author contributions: All authors performed the bibliographic analysis and wrote the paper.
Conflict-of-interest statement: All authors have no conflict of interest related to the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Clara Steichen, PhD, Postdoctoral Fellow, INSERM U1082 IRTOMIT, CHU de Poitiers, 2 rue de la Milétrie, Poitiers F-86021, France. clara.steichen@inserm.fr
Telephone: +33-549-443089 Fax: +33-549-444922
Received: March 14, 2019
Peer-review started: March 15, 2019
First decision: June 5, 2019
Revised: June 13, 2019
Accepted: July 29, 2019
Article in press: July 29, 2019
Published online: October 26, 2019
Processing time: 223 Days and 19.9 Hours
Abstract

Ten years after the initial generation of induced pluripotent stem cells (hiPSCs) from human tissues, their potential is no longer questioned, with over 15000 publications listed on PubMed, covering various fields of research; including disease modeling, cell therapy strategies, pharmacology/toxicology screening and 3D organoid systems. However, despite evidences that the presence of mutations in hiPSCs should be a concern, publications addressing genomic integrity of these cells represent less than 1% of the literature. After a first overview of the mutation types currently reported in hiPSCs, including karyotype abnormalities, copy number variations, single point mutation as well as uniparental disomy, this review will discuss the impact of reprogramming parameters such as starting cell type and reprogramming method on the maintenance of the cellular genomic integrity. Then, a specific focus will be placed on culture conditions and subsequent differentiation protocols and how their may also trigger genomic aberrations within the cell population of interest. Finally, in a last section, the impact of genomic alterations on the possible usages of hiPSCs and their derivatives will also be exemplified and discussed. We will also discuss which techniques or combination of techniques should be used to screen for genomic abnormalities with a particular focus on the necessary quality controls and the potential alternatives.

Keywords: Induced pluripotent stem cells; Genomic integrity; Mutations; Karyotype; Differentiation; Cell therapy; Quality control; Reprogramming

Core tip: The potential of human induced pluripotent stem cells (hiPSCs) is no longer questioned, with applications in many fields including disease modeling and cell therapy. However, the presence of mutations in hiPSCs is a concern. After a first overview of the mutation types currently reported in hiPSCs, this review is aimed at discussing the important points to understand and possibly control the occurrence of mutations during hiPSCs reprogramming, long term culture but also differentiation. Finally, the impact of genomic alterations on the possible usages of hiPSC derivatives will be discussed, with a focus on the necessary quality controls and the potential alternatives.