Cargando…
Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells
Human pluripotent stem cells, including cloned embryonic and induced pluripotent stem cells, offer a limitless cellular source for regenerative medicine. However, their derivation efficiency is limited, and a large proportion of cells are arrested during reprogramming. In the current study, we explo...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428033/ https://www.ncbi.nlm.nih.gov/pubmed/25965553 http://dx.doi.org/10.1038/srep10114 |
_version_ | 1782370826391126016 |
---|---|
author | Yu, Yang Chang, Liang Zhao, Hongcui Li, Rong Fan, Yong Qiao, Jie |
author_facet | Yu, Yang Chang, Liang Zhao, Hongcui Li, Rong Fan, Yong Qiao, Jie |
author_sort | Yu, Yang |
collection | PubMed |
description | Human pluripotent stem cells, including cloned embryonic and induced pluripotent stem cells, offer a limitless cellular source for regenerative medicine. However, their derivation efficiency is limited, and a large proportion of cells are arrested during reprogramming. In the current study, we explored chromosome microdeletion/duplication in arrested and established reprogrammed cells. Our results show that aneuploidy induced by somatic cell nuclear transfer technology is a key factor in the developmental failure of cloned human embryos and primary colonies from implanted cloned blastocysts and that expression patterns of apoptosis-related genes are dynamically altered. Overall, ~20%–53% of arrested primary colonies in induced plurpotent stem cells displayed aneuploidy, and upregulation of P53 and Bax occurred in all arrested primary colonies. Interestingly, when somatic cells with pre-existing chromosomal mutations were used as donor cells, no cloned blastocysts were obtained, and additional chromosomal mutations were detected in the resulting iPS cells following long-term culture, which was not observed in the two iPS cell lines with normal karyotypes. In conclusion, aneuploidy induced by the reprogramming process restricts the derivation of pluripotent stem cells, and, more importantly, pre-existing chromosomal mutations enhance the risk of genome instability, which limits the clinical utility of these cells. |
format | Online Article Text |
id | pubmed-4428033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44280332015-05-21 Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells Yu, Yang Chang, Liang Zhao, Hongcui Li, Rong Fan, Yong Qiao, Jie Sci Rep Article Human pluripotent stem cells, including cloned embryonic and induced pluripotent stem cells, offer a limitless cellular source for regenerative medicine. However, their derivation efficiency is limited, and a large proportion of cells are arrested during reprogramming. In the current study, we explored chromosome microdeletion/duplication in arrested and established reprogrammed cells. Our results show that aneuploidy induced by somatic cell nuclear transfer technology is a key factor in the developmental failure of cloned human embryos and primary colonies from implanted cloned blastocysts and that expression patterns of apoptosis-related genes are dynamically altered. Overall, ~20%–53% of arrested primary colonies in induced plurpotent stem cells displayed aneuploidy, and upregulation of P53 and Bax occurred in all arrested primary colonies. Interestingly, when somatic cells with pre-existing chromosomal mutations were used as donor cells, no cloned blastocysts were obtained, and additional chromosomal mutations were detected in the resulting iPS cells following long-term culture, which was not observed in the two iPS cell lines with normal karyotypes. In conclusion, aneuploidy induced by the reprogramming process restricts the derivation of pluripotent stem cells, and, more importantly, pre-existing chromosomal mutations enhance the risk of genome instability, which limits the clinical utility of these cells. Nature Publishing Group 2015-05-12 /pmc/articles/PMC4428033/ /pubmed/25965553 http://dx.doi.org/10.1038/srep10114 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Yu, Yang Chang, Liang Zhao, Hongcui Li, Rong Fan, Yong Qiao, Jie Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells |
title | Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells |
title_full | Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells |
title_fullStr | Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells |
title_full_unstemmed | Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells |
title_short | Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells |
title_sort | chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428033/ https://www.ncbi.nlm.nih.gov/pubmed/25965553 http://dx.doi.org/10.1038/srep10114 |
work_keys_str_mv | AT yuyang chromosomemicroduplicationinsomaticcellsdecreasesthegeneticstabilityofhumanreprogrammedsomaticcellsandresultsinpluripotentstemcells AT changliang chromosomemicroduplicationinsomaticcellsdecreasesthegeneticstabilityofhumanreprogrammedsomaticcellsandresultsinpluripotentstemcells AT zhaohongcui chromosomemicroduplicationinsomaticcellsdecreasesthegeneticstabilityofhumanreprogrammedsomaticcellsandresultsinpluripotentstemcells AT lirong chromosomemicroduplicationinsomaticcellsdecreasesthegeneticstabilityofhumanreprogrammedsomaticcellsandresultsinpluripotentstemcells AT fanyong chromosomemicroduplicationinsomaticcellsdecreasesthegeneticstabilityofhumanreprogrammedsomaticcellsandresultsinpluripotentstemcells AT qiaojie chromosomemicroduplicationinsomaticcellsdecreasesthegeneticstabilityofhumanreprogrammedsomaticcellsandresultsinpluripotentstemcells |