Few Single Nucleotide Variations in Exomes of Human Cord Blood Induced Pluripotent Stem Cells

Rui Jun Su, Yadong Yang, Amanda Neises, Kimberly J. Payne, Jasmin Wang, Kasthuribai Viswanathan, Edward K. Wakeland, Xiangdong Fang, Xiao Bing Zhang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The effect of the cellular reprogramming process per se on mutation load remains unclear. To address this issue, we performed whole exome sequencing analysis of induced pluripotent stem cells (iPSCs) reprogrammed from human cord blood (CB) CD34+ cells. Cells from a single donor and improved lentiviral vectors for high-efficiency (2-14%) reprogramming were used to examine the effects of three different combinations of reprogramming factors: OCT4 and SOX2 (OS), OS and ZSCAN4 (OSZ), OS and MYC and KLF4 (OSMK). Five clones from each group were subject to whole exome sequencing analysis. We identified 14, 11, and 9 single nucleotide variations (SNVs), in exomes, including untranslated regions (UTR), in the five clones of OSMK, OS, and OSZ iPSC lines. Only 8, 7, and 4 of these, respectively, were protein-coding mutations. An average of 1.3 coding mutations per CB iPSC line is remarkably lower than previous studies using fibroblasts and low-efficiency reprogramming approaches. These data demonstrate that point nucleotide mutations during cord blood reprogramming are negligible and that the inclusion of genome stabilizers like ZSCAN4 during reprogramming may further decrease reprogramming-associated mutations. Our findings provide evidence that CB is a superior source of cells for iPSC banking.

Original languageEnglish (US)
Article numbere59908
JournalPloS one
Volume8
Issue number4
DOIs
StatePublished - Apr 1 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Su, R. J., Yang, Y., Neises, A., Payne, K. J., Wang, J., Viswanathan, K., Wakeland, E. K., Fang, X., & Zhang, X. B. (2013). Few Single Nucleotide Variations in Exomes of Human Cord Blood Induced Pluripotent Stem Cells. PloS one, 8(4), [e59908]. https://doi.org/10.1371/journal.pone.0059908