Halliwell, J.A., Frith, T.J.R., Laing, O. et al. (8 more authors) (2020) Nucleosides rescue replication-mediated genome instability of human pluripotent stem cells. Stem Cell Reports, 14 (6). pp. 1009-1017. ISSN 2213-6711
Abstract
Human pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | pluripotent; DNA; damage; replication; stress; nucleosides; mitotic; errors; human |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Funding Information: | Funder Grant number EUROPEAN COMMISSION - HORIZON 2020 668724 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Jun 2020 10:01 |
Last Modified: | 15 Jun 2020 10:01 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.stemcr.2020.04.004 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:161530 |