LINE-1 (long interspersed element-1) 逆转录转座子在试管中和在小鼠脑中已知能够穿过成年大鼠神经前体细胞(NPCs)的基因组。
现在,研究表明,从人胎儿脑中分离出的以及从人胚胎干细胞演变来的NPCs,在试管中还支持人工培养的人LINE-1s发生逆转录转座。有趣的是,当与来自同一人的心脏或肝脏基因组DNA中的内生LINE-1s版本数量相比时,会发现成人脑中海马体和其他地方中的内生LINE-1s版本数量有所增加。这表明,LINE-1逆转录转座事件也许有助于脑中基因表达的不同体细胞镶嵌性和异质性。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 460, 1127-1131 (27 August 2009) | doi:10.1038/nature08248
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.