Pluripotent cells display enhanced resistance to mutagenesis

Daniel J. Cooper, I. Chung Chen, Christine Hernandez, Yufeng Wang, Christi A Walter, John R. McCarrey

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Pluripotent cells have been reported to exhibit lower frequencies of point mutations and higher levels of DNA repair than differentiated cells. This predicts that pluripotent cells are less susceptible to mutagenic exposures than differentiated cells. To test this prediction, we used a lacI mutation-reporter transgene system to assess the frequency of point mutations in multiple lines of mouse pluripotent embryonic stem cells and induced pluripotent cells, as well as in multiple lines of differentiated fibroblast cells, before and after exposure to a moderate dose of the mutagen, methyl methanesulfonate. We also measured levels of key enzymes in the base excision repair (BER) pathway in each cell line before and after exposure to the mutagen. Our results confirm that pluripotent cells normally maintain lower frequencies of point mutations than differentiated cells, and show that differentiated cells exhibit a large increase in mutation frequency following a moderate mutagenic exposure, whereas pluripotent cells subjected to the same exposure show no increase in mutations. This result likely reflects the higher levels of BER proteins detectable in pluripotent cells prior to exposure and supports our thesis that maintenance of enhanced genetic integrity is a fundamental characteristic of pluripotent cells.

Original languageEnglish (US)
Pages (from-to)113-117
Number of pages5
JournalStem Cell Research
Volume19
DOIs
StatePublished - Mar 1 2017

Keywords

  • Base excision repair
  • DNA repair
  • Epigenetic programming
  • Stem cells

ASJC Scopus subject areas

  • Medicine(all)
  • Developmental Biology
  • Cell Biology

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    Cooper, D. J., Chen, I. C., Hernandez, C., Wang, Y., Walter, C. A., & McCarrey, J. R. (2017). Pluripotent cells display enhanced resistance to mutagenesis. Stem Cell Research, 19, 113-117. https://doi.org/10.1016/j.scr.2016.12.029