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DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells

The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that scree...

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Autores principales: Luo, Li Z., Gopalakrishna-Pillai, Sailesh, Nay, Stephanie L., Park, Sang-Won, Bates, Steven E., Zeng, Xianmin, Iverson, Linda E., O'Connor, Timothy R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295811/
https://www.ncbi.nlm.nih.gov/pubmed/22412831
http://dx.doi.org/10.1371/journal.pone.0030541
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author Luo, Li Z.
Gopalakrishna-Pillai, Sailesh
Nay, Stephanie L.
Park, Sang-Won
Bates, Steven E.
Zeng, Xianmin
Iverson, Linda E.
O'Connor, Timothy R.
author_facet Luo, Li Z.
Gopalakrishna-Pillai, Sailesh
Nay, Stephanie L.
Park, Sang-Won
Bates, Steven E.
Zeng, Xianmin
Iverson, Linda E.
O'Connor, Timothy R.
author_sort Luo, Li Z.
collection PubMed
description The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that screening/characterization of possible repair deficiencies in pluripotent human stem cells should be a necessary step prior to their clinical and research use. In this study, a comparison of DNA repair pathways in pluripotent cells, as compared to those in non-pluripotent cells, demonstrated that DNA repair capacities of pluripotent cell lines were more heterogeneous than those of differentiated lines examined and were generally greater. Although pluripotent cells had high DNA repair capacities for nucleotide excision repair, we show that ultraviolet radiation at low fluxes induced an apoptotic response in these cells, while differentiated cells lacked response to this stimulus, and note that pluripotent cells had a similar apoptotic response to alkylating agent damage. This sensitivity of pluripotent cells to damage is notable since viable pluripotent cells exhibit less ultraviolet light-induced DNA damage than do differentiated cells that receive the same flux. In addition, the importance of screening pluripotent cells for DNA repair defects was highlighted by an iPSC line that demonstrated a normal spectral karyotype, but showed both microsatellite instability and reduced DNA repair capacities in three out of four DNA repair pathways examined. Together, these results demonstrate a need to evaluate DNA repair capacities in pluripotent cell lines, in order to characterize their genomic stability, prior to their pre-clinical and clinical use.
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spelling pubmed-32958112012-03-12 DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells Luo, Li Z. Gopalakrishna-Pillai, Sailesh Nay, Stephanie L. Park, Sang-Won Bates, Steven E. Zeng, Xianmin Iverson, Linda E. O'Connor, Timothy R. PLoS One Research Article The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that screening/characterization of possible repair deficiencies in pluripotent human stem cells should be a necessary step prior to their clinical and research use. In this study, a comparison of DNA repair pathways in pluripotent cells, as compared to those in non-pluripotent cells, demonstrated that DNA repair capacities of pluripotent cell lines were more heterogeneous than those of differentiated lines examined and were generally greater. Although pluripotent cells had high DNA repair capacities for nucleotide excision repair, we show that ultraviolet radiation at low fluxes induced an apoptotic response in these cells, while differentiated cells lacked response to this stimulus, and note that pluripotent cells had a similar apoptotic response to alkylating agent damage. This sensitivity of pluripotent cells to damage is notable since viable pluripotent cells exhibit less ultraviolet light-induced DNA damage than do differentiated cells that receive the same flux. In addition, the importance of screening pluripotent cells for DNA repair defects was highlighted by an iPSC line that demonstrated a normal spectral karyotype, but showed both microsatellite instability and reduced DNA repair capacities in three out of four DNA repair pathways examined. Together, these results demonstrate a need to evaluate DNA repair capacities in pluripotent cell lines, in order to characterize their genomic stability, prior to their pre-clinical and clinical use. Public Library of Science 2012-03-06 /pmc/articles/PMC3295811/ /pubmed/22412831 http://dx.doi.org/10.1371/journal.pone.0030541 Text en Luo et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Luo, Li Z.
Gopalakrishna-Pillai, Sailesh
Nay, Stephanie L.
Park, Sang-Won
Bates, Steven E.
Zeng, Xianmin
Iverson, Linda E.
O'Connor, Timothy R.
DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells
title DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells
title_full DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells
title_fullStr DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells
title_full_unstemmed DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells
title_short DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells
title_sort dna repair in human pluripotent stem cells is distinct from that in non-pluripotent human cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295811/
https://www.ncbi.nlm.nih.gov/pubmed/22412831
http://dx.doi.org/10.1371/journal.pone.0030541
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