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L1 retrotransposition in human neural progenitor cells
Nicole G. Coufal1, José L. Garcia-Perez2,3, Grace E. Peng1, Gene W. Yeo1,6, Yangling Mu1, Michael T. Lovci1,6, Maria Morell4, K. Sue O'Shea4, John V. Moran2,5 & Fred H. Gage1
1 Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
2 Departments of Human Genetics and Internal Medicine, 1241 East Catherine Street, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618, USA
3 Andalusian Stem Cell Bank, Center for Biomedical Research, Avda Conocimiento s/n, University of Granada, 18100, Spain
4 Department of Cell and Developmental Biology, 109 Zina Pitcher, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA
5 Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789, USA
6 Present address: Stem Cell Program, Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-5004, USA.
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 1. 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.
