LINE-1 (long interspersed element-1) 逆轉(zhuǎn)錄轉(zhuǎn)座子在試管中和在小鼠腦中已知能夠穿過成年大鼠神經(jīng)前體細(xì)胞(NPCs)的基因組,。
現(xiàn)在,,研究表明,從人胎兒腦中分離出的以及從人胚胎干細(xì)胞演變來的NPCs,在試管中還支持人工培養(yǎng)的人LINE-1s發(fā)生逆轉(zhuǎn)錄轉(zhuǎn)座。有趣的是,當(dāng)與來自同一人的心臟或肝臟基因組DNA中的內(nèi)生LINE-1s版本數(shù)量相比時(shí),,會(huì)發(fā)現(xiàn)成人腦中海馬體和其他地方中的內(nèi)生LINE-1s版本數(shù)量有所增加。這表明,LINE-1逆轉(zhuǎn)錄轉(zhuǎn)座事件也許有助于腦中基因表達(dá)的不同體細(xì)胞鑲嵌性和異質(zhì)性,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.