L1 retrotransposition in human neural progenitor cells

Nicole G Coufal, José L Garcia-Perez, Grace E Peng, Gene W Yeo, Yangling Mu, Michael T Lovci, Maria Morell, K Sue O'Shea, John V Moran, Fred H Gage

Research output: Contribution to journalArticlepeer-review

Abstract

Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo. Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.

Original languageEnglish
Pages (from-to)1127-31
Number of pages5
JournalNature
Volume460
Issue number7259
DOIs
Publication statusPublished - 27 Aug 2009

Keywords

  • 5' Untranslated Regions
  • Brain
  • Cell Line
  • Chromatin Immunoprecipitation
  • DNA Methylation
  • Embryonic Stem Cells
  • Fetus
  • Gene Dosage
  • Humans
  • Neurons
  • Polymerase Chain Reaction
  • Retroelements

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