L1 retrotransposition in human neural progenitor cells.
L1 retrotransposition in human neural progenitor cells.
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作者：
长散布元件-1（LINE-1或L1）逆转录转座子对人类基因组产生了巨大影响。L1必须在生殖系或早期发育过程中逆转录，以确保其进化成功;然而，这一过程对体细胞的影响程度尚不清楚。我们以前证明，工程人类L1可以逆转录转座在成年大鼠海马祖细胞（NPC）在体外和小鼠大脑在体内。在这里，我们证明了从人胎脑分离的NPC和来自人胚胎干细胞（hESC）的NPC支持体外工程化人L1的逆转录转座。此外，我们开发了一种定量多重聚合酶链反应，检测到增加的内源性L1的拷贝数在海马和成年人大脑的几个区域相比，内源性L1的拷贝数在心脏或肝脏基因组DNA从同一个供体。这些数据表明，从头L1逆转录转座事件可能发生在人脑中，原则上，有可能有助于个人体细胞镶嵌。
Long Interspersed Element-1 (LINE-1 or L1) retrotransposons have dramatically impacted 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 impacts somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells (NPCs) in vitro and in the mouse brain in vivo. Here, we demonstrate that NPCs isolated from human fetal brain and NPCs derived from human embryonic stem cells (hESCs) 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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影响因子：
64.8
作者：
Muotri, AR;Chu, VT;Gage, FH
通讯作者：
Gage, FH
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
64.5
作者：
Symer, DE;Connelly, C;Boeke, JD
通讯作者：
Boeke, JD
影响因子：
3.5
作者：
Kulpa, DA;Moran, JV
通讯作者：
Moran, JV
影响因子：
9.8
作者：
Myers, JS;Vincent, BJ;Batzer, MA
通讯作者：
Batzer, MA