title: Antioxidant supplementation reduces genomic aberrations in human induced pluripotent stem cells.
abstract: Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using oncogenic transcription factors. However, this method leads to genetic aberrations in iPSCs via unknown mechanisms, which may limit their clinical use. Here, we demonstrate that the supplementation of growth media with antioxidants reduces the genome instability of cells transduced with the reprogramming factors. Antioxidant supplementation did not affect transgene expression level or silencing kinetics. Importantly, iPSCs made with antioxidants had significantly fewer de novo copy number variations, but not fewer coding point mutations, than iPSCs made without antioxidants. Our results suggest that the quality and safety of human iPSCs might be enhanced by using antioxidants in the growth media during the generation and maintenance of iPSCs.
authors: Ontario Institute for Cancer Research, 101 College Street, Toronto, Canada M5G 0A3 ; Research Center of Stem Cell and Developmental Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors: Junfeng
authors: J
authors: Ji
authors: Ontario Institute for Cancer Research, 101 College Street, Toronto, Canada M5G 0A3 ; National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Vivek
authors: V
authors: Sharma
authors: Research Center of Stem Cell and Developmental Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors: Suxia
authors: S
authors: Qi
authors: Research Center of Stem Cell and Developmental Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors: Meritxell Espino
authors: ME
authors: Guarch
authors: Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China.
authors: Ping
authors: P
authors: Zhao
authors: Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China.
authors: Zhiwei
authors: Z
authors: Luo
authors: Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China.
authors: Wenxia
authors: W
authors: Fan
authors: Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China.
authors: Yu
authors: Y
authors: Wang
authors: Ontario Institute for Cancer Research, 101 College Street, Toronto, Canada M5G 0A3.
authors: Faridah
authors: F
authors: Mbabaali
authors: Ontario Institute for Cancer Research, 101 College Street, Toronto, Canada M5G 0A3.
authors: Dante
authors: D
authors: Neculai
authors: Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China.
authors: Miguel Angel
authors: MA
authors: Esteban
authors: Ontario Institute for Cancer Research, 101 College Street, Toronto, Canada M5G 0A3.
authors: John D
authors: JD
authors: McPherson
authors: Ontario Institute for Cancer Research, 101 College Street, Toronto, Canada M5G 0A3 ; Department of Medical Biophysics, University of Toronto, Toronto, Canada M5G 2M9.
authors: Nizar N
authors: NN
authors: Batada
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D042822:Genomic Instability; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014157:Transcription Factors