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Transdifferentiation of Mouse Embryonic Fibroblasts into Dopaminergic Neurons Reactivates LINE-1 Repetitive Elements.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-01-02 , DOI: 10.1016/j.stemcr.2019.12.002
Francesco Della Valle 1 , Manjula P Thimma 1 , Massimiliano Caiazzo 2 , Salvatore Pulcrano 3 , Mirko Celii 1 , Sabir A Adroub 1 , Peng Liu 1 , Gregorio Alanis-Lobato 4 , Vania Broccoli 5 , Valerio Orlando 1
Affiliation  

In mammals, LINE-1 (L1) retrotransposons constitute between 15% and 20% of the genome. Although only a few copies have retained the ability to retrotranspose, evidence in brain and differentiating pluripotent cells indicates that L1 retrotransposition occurs and creates mosaics in normal somatic tissues. The function of de novo insertions remains to be understood. The transdifferentiation of mouse embryonic fibroblasts to dopaminergic neuronal fate provides a suitable model for studying L1 dynamics in a defined genomic and unaltered epigenomic background. We found that L1 elements are specifically re-expressed and mobilized during the initial stages of reprogramming and that their insertions into specific acceptor loci coincides with higher chromatin accessibility and creation of new transcribed units. Those events accompany the maturation of neuronal committed cells. We conclude that L1 retrotransposition is a non-random process correlating with chromatin opening and lncRNA production that accompanies direct somatic cell reprogramming.



中文翻译:

小鼠胚胎成纤维细胞向多巴胺能神经元的转分化激活LINE-1重复元件。

在哺乳动物中,LINE-1(L1)逆转座子占基因组的15%至20%。尽管只有少数拷贝保留了逆转座的能力,但脑和分化多能细胞中的证据表明发生了L1逆转座,并在正常的体细胞组织中形成了花叶。从头开始的功能插入仍有待理解。小鼠胚胎成纤维细胞向多巴胺能神经元命运的转分化提供了一个合适的模型,用于在确定的基因组和不变的表观基因组背景下研究L1动力学。我们发现,L1元件在重新编程的初始阶段被特别地表达和动员,并且它们插入特定受体基因座的过程与更高的染色质可及性和新转录单位的创建相吻合。这些事件伴随着神经元定型细胞的成熟。我们得出结论,L1逆转座是与染色质开放和伴随直接体细胞重编程的lncRNA产生相关的非随机过程。

更新日期:2020-01-02
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