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

14 Citations (Scopus)

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

Fingerprint

Exome
Induced Pluripotent Stem Cells
Stem cells
Fetal Blood
Blood
Nucleotides
nucleotides
mutation
Mutation
blood
Clone Cells
Untranslated Regions
Cell Line
cell lines
clones
Fibroblasts
banking
Point Mutation
Blood Cells
blood cells

ASJC Scopus subject areas

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

Cite this

Su, R. J., Yang, Y., Neises, A., Payne, K. J., Wang, J., Viswanathan, K., ... 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

Few Single Nucleotide Variations in Exomes of Human Cord Blood Induced Pluripotent Stem Cells. / Su, Rui Jun; Yang, Yadong; Neises, Amanda; Payne, Kimberly J.; Wang, Jasmin; Viswanathan, Kasthuribai; Wakeland, Edward K.; Fang, Xiangdong; Zhang, Xiao Bing.

In: PLoS One, Vol. 8, No. 4, e59908, 01.04.2013.

Research output: Contribution to journalArticle

Su, RJ, Yang, Y, Neises, A, Payne, KJ, Wang, J, Viswanathan, K, Wakeland, EK, Fang, X & Zhang, XB 2013, 'Few Single Nucleotide Variations in Exomes of Human Cord Blood Induced Pluripotent Stem Cells', PLoS One, vol. 8, no. 4, e59908. https://doi.org/10.1371/journal.pone.0059908
Su, Rui Jun ; Yang, Yadong ; Neises, Amanda ; Payne, Kimberly J. ; Wang, Jasmin ; Viswanathan, Kasthuribai ; Wakeland, Edward K. ; Fang, Xiangdong ; Zhang, Xiao Bing. / Few Single Nucleotide Variations in Exomes of Human Cord Blood Induced Pluripotent Stem Cells. In: PLoS One. 2013 ; Vol. 8, No. 4.
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