Cargando…

p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming

Human induced pluripotent stem (iPS) cells have great potential in regenerative medicine, but this depends on the integrity of their genomes. iPS cells have been found to contain a large number of de novo genetic alterations due to DNA damage response during reprogramming. Thus, to maintain the gene...

Descripción completa

Detalles Bibliográficos
Autores principales: Gong, Lu, Pan, Xiao, Chen, Haide, Rao, Lingjun, Zeng, Yelin, Hang, Honghui, Peng, Jinrong, Xiao, Lei, Chen, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118801/
https://www.ncbi.nlm.nih.gov/pubmed/27874035
http://dx.doi.org/10.1038/srep37281
_version_ 1782468995574661120
author Gong, Lu
Pan, Xiao
Chen, Haide
Rao, Lingjun
Zeng, Yelin
Hang, Honghui
Peng, Jinrong
Xiao, Lei
Chen, Jun
author_facet Gong, Lu
Pan, Xiao
Chen, Haide
Rao, Lingjun
Zeng, Yelin
Hang, Honghui
Peng, Jinrong
Xiao, Lei
Chen, Jun
author_sort Gong, Lu
collection PubMed
description Human induced pluripotent stem (iPS) cells have great potential in regenerative medicine, but this depends on the integrity of their genomes. iPS cells have been found to contain a large number of de novo genetic alterations due to DNA damage response during reprogramming. Thus, to maintain the genetic stability of iPS cells is an important goal in iPS cell technology. DNA damage response can trigger tumor suppressor p53 activation, which ensures genome integrity of reprogramming cells by inducing apoptosis and senescence. p53 isoform Δ133p53 is a p53 target gene and functions to not only antagonize p53 mediated apoptosis, but also promote DNA double-strand break (DSB) repair. Here we report that Δ133p53 is induced in reprogramming. Knockdown of Δ133p53 results 2-fold decrease in reprogramming efficiency, 4-fold increase in chromosomal aberrations, whereas overexpression of Δ133p53 with 4 Yamanaka factors showes 4-fold increase in reprogamming efficiency and 2-fold decrease in chromosomal aberrations, compared to those in iPS cells induced only with 4 Yamanaka factors. Overexpression of Δ133p53 can inhibit cell apoptosis and promote DNA DSB repair foci formation during reprogramming. Our finding demonstrates that the overexpression of Δ133p53 not only enhances reprogramming efficiency, but also results better genetic quality in iPS cells.
format Online
Article
Text
id pubmed-5118801
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-51188012016-11-28 p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming Gong, Lu Pan, Xiao Chen, Haide Rao, Lingjun Zeng, Yelin Hang, Honghui Peng, Jinrong Xiao, Lei Chen, Jun Sci Rep Article Human induced pluripotent stem (iPS) cells have great potential in regenerative medicine, but this depends on the integrity of their genomes. iPS cells have been found to contain a large number of de novo genetic alterations due to DNA damage response during reprogramming. Thus, to maintain the genetic stability of iPS cells is an important goal in iPS cell technology. DNA damage response can trigger tumor suppressor p53 activation, which ensures genome integrity of reprogramming cells by inducing apoptosis and senescence. p53 isoform Δ133p53 is a p53 target gene and functions to not only antagonize p53 mediated apoptosis, but also promote DNA double-strand break (DSB) repair. Here we report that Δ133p53 is induced in reprogramming. Knockdown of Δ133p53 results 2-fold decrease in reprogramming efficiency, 4-fold increase in chromosomal aberrations, whereas overexpression of Δ133p53 with 4 Yamanaka factors showes 4-fold increase in reprogamming efficiency and 2-fold decrease in chromosomal aberrations, compared to those in iPS cells induced only with 4 Yamanaka factors. Overexpression of Δ133p53 can inhibit cell apoptosis and promote DNA DSB repair foci formation during reprogramming. Our finding demonstrates that the overexpression of Δ133p53 not only enhances reprogramming efficiency, but also results better genetic quality in iPS cells. Nature Publishing Group 2016-11-22 /pmc/articles/PMC5118801/ /pubmed/27874035 http://dx.doi.org/10.1038/srep37281 Text en Copyright © 2016, The Author(s) 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
Gong, Lu
Pan, Xiao
Chen, Haide
Rao, Lingjun
Zeng, Yelin
Hang, Honghui
Peng, Jinrong
Xiao, Lei
Chen, Jun
p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
title p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
title_full p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
title_fullStr p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
title_full_unstemmed p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
title_short p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
title_sort p53 isoform δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118801/
https://www.ncbi.nlm.nih.gov/pubmed/27874035
http://dx.doi.org/10.1038/srep37281
work_keys_str_mv AT gonglu p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT panxiao p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT chenhaide p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT raolingjun p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT zengyelin p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT hanghonghui p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT pengjinrong p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT xiaolei p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming
AT chenjun p53isoformd133p53promotesefficiencyofinducedpluripotentstemcellsandensuresgenomicintegrityduringreprogramming