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

View/ Open
Author
Pan, Xiao
Chen, Haide
Rao, Lingjun
Zeng, Yelin
Hang, Honghui
Peng, Jinrong
Xiao, Lei
Chen, Jun
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/srep37281Metadata
Show full item recordCitation
Gong, Lu, Xiao Pan, Haide Chen, Lingjun Rao, Yelin Zeng, Honghui Hang, Jinrong Peng, Lei Xiao, and Jun Chen. 2016. “p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming.” Scientific Reports 6 (1): 37281. doi:10.1038/srep37281. http://dx.doi.org/10.1038/srep37281.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118801/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626170
Collections
- SPH Scholarly Articles [6399]
Contact administrator regarding this item (to report mistakes or request changes)