title: p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming.
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.
authors.affiliation: Key laboratory for Molecular Animal Nutrition, Ministry of Education, Innovation Center for Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.|Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Gong
authors.affiliation: Key laboratory for Molecular Animal Nutrition, Ministry of Education, Innovation Center for Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Pan
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Haide
authors.initials: H
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Rao
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yelin
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, State Key Laboratory Breeding Base of Eco-Environments and Bio-Resources of the Three Gorges Reservoir Region, School of Life Sciences, Southwest University, 2 Tiansheng Road, Beibei, Chongqing, 400715 China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Hang
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Peng
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Key laboratory for Molecular Animal Nutrition, Ministry of Education, Innovation Center for Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000067470:Cellular Reprogramming Techniques; D042822:Genomic Instability; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53