Article

L1 retrotransposition in human neural progenitor cells

Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature (Impact Factor: 42.35). 09/2009; 460(7259):1127-31. DOI: 10.1038/nature08248
Source: PubMed

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.

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Available from: Nicole G Coufal, Aug 19, 2015
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    • "Previously, evidence for L1 insertions in normal somatic cells has come from two sources. A number of studies have shown that somatic L1 insertions occur in neuronal development and are present in various sites in the human and mouse brain (Muotri et al. 2005; Coufal et al. 2009; Baillie et al. 2011; Evrony et al. 2012; Upton et al. 2015). Moreover, a small number of examples of L1, SVA, and processed pseudogene insertion have been reported to occur in early human development (van den Hurk et al. 2007; de Boer et al. 2014; Vogt et al. 2014). "
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    • "There is also evidence that retroelements and transposons are highly active during brain development and in neural progenitor cells (NPCs) (Muotri et al., 2005, 2010; Baillie et al., 2011; Evrony et al., 2012; Li et al., 2013; Perrat et al., 2013). For example, LINE-1 elements have been found to be transcriptionally active and to retrotranspose in NPCs (Muotri et al., 2005, 2010; Coufal et al., 2009). In addition, we have previously found that deletion of TRIM28 in postmitotic forebrain neurons results in complex behavioral alterations, including vulnerability to stress (Jakobsson et al., 2008). "
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    • "In E. cyanostictus brain, each sex overexpressed a different class of transposable elements: A polinton DNA transposon in females and a gypsy retrotransposon in males. Active transposable elements in the brain have been associated with aging and neuronal decline (Coufal et al. 2009; Li et al. 2013). "
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