Coufal Nicole G, Garcia-Perez José L, Peng Grace E, Yeo Gene W, Mu Yangling, Lovci Michael T, Morell Maria, O'Shea K Sue, Moran John V, Gage Fred H
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature. 2009 Aug 27;460(7259):1127-31. doi: 10.1038/nature08248. Epub 2009 Aug 5.
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.
长散在核元件1（LINE-1或L1）逆转座子对人类基因组产生了显著影响。L1必须在生殖系或早期发育过程中进行逆转座，以确保其在进化上的成功，然而这一过程对体细胞的影响程度却鲜为人知。我们之前证明，工程化的人类L1能够在体外的成年大鼠海马祖细胞以及体内的小鼠大脑中进行逆转座。在此，我们证明从人类胎儿大脑分离并源自人类胚胎干细胞的神经祖细胞在体外支持工程化人类L1的逆转座。此外，我们开发了一种定量多重聚合酶链反应，与来自同一供体的心脏或肝脏基因组DNA中的内源性L1拷贝数相比，该反应检测到成年人类大脑的海马及几个区域内源性L1的拷贝数增加。这些数据表明，新生L1逆转座事件可能发生在人类大脑中，并且原则上有可能导致个体体细胞嵌合现象。
