L1 retrotransposition in human neural progenitor cells

Abstract

It is known that LINE-1 (long interspersed element-1) retrotransposons can move throughout the genomes of adult rat neural progenitor cells (NPCs) in vitro and in the mouse brain. Now it is shown that NPCs isolated from human fetal brain and derived from human embryonic stem cells also support the retrotransposition of engineered human LINE-1s in vitro. Interestingly, there is an increase in the copy number of endogenous LINE-1s in the hippocampus and elsewhere in adult human brains when compared to the copy number of endogenous LINE-1s in heart or liver genomic DNA from the same individual. This suggests that LINE-1 retrotransposition events may contribute to individual somatic mosaicism and heterogeneity of gene expression in the brain. Long interspersed element 1 (LINE-1 or L1) retrotransposons have been shown to move throughout the genomes of adult rat neural progenitor cells (NPCs) in vitro and in the mouse brain. Here, NPCs isolated from human fetal brain and derived from human embryonic stem cells are shown to support the retrotransposition of engineered human L1s in vitro, which could contribute to individual somatic mosaicism. 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 vivo1. 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.