小柯机器人

韩国科学技术院Young Seok Ju等研究人员合作发现，正常结直肠上皮细胞中广泛存在体细胞L1逆转录转座。相关论文于2023年5月10日在线发表在《自然》杂志上。

研究人员探索了从28个人的三种不同类型的细胞中收集的899个单细胞克隆的全基因组序列。研究人员确定了1708个体细胞长穿插核元件-1（L1）逆转录转座事件，这些事件在结直肠上皮细胞中富集，并与年龄呈正相关。源元件的指纹图谱显示有34个具有逆转录转座能力的L1。

多维分析表明：（1）体细胞L1逆转录从早期胚胎发育开始就以相当高的速度发生，（2）源元件的表观遗传学开/关优先决定于早期器官发育阶段，（3）逆转录能力强的L1，其群体等位基因频率较低，逆转录转座活性较高，（4）细胞质中的L1转录本只有一小部分最终在体细胞中被逆转录。对匹配的癌症的分析进一步表明，在结直肠肿瘤发生过程中，体细胞L1逆转录转座率大大增加。

总之，这项研究说明了L1逆转录转座引发的正常细胞中的体细胞镶嵌，并提供了关于人类一生中可转座元件的基因组和表观基因组调控的见解。

据悉，在一个人的一生中，基因组的改变会在体细胞中积累。然而，人类基因组中广泛存在的移动元件（L1）的逆转录转座所引起的突变情况在正常细胞中还不甚明了。

附：英文原文

Title: Widespread somatic L1 retrotransposition in normal colorectal epithelium

Author: Nam, Chang Hyun, Youk, Jeonghwan, Kim, Jeong Yeon, Lim, Joonoh, Park, Jung Woo, Oh, Soo A, Lee, Hyun Jung, Park, Ji Won, Won, Hyein, Lee, Yunah, Jeong, Seung-Yong, Lee, Dong-Sung, Oh, Ji Won, Han, Jinju, Lee, Junehawk, Kwon, Hyun Woo, Kim, Min Jung, Ju, Young Seok

Issue&Volume: 2023-05-10

Abstract: Throughout an individual’s lifetime, genomic alterations accumulate in somatic cells1,2,3,4,5,6,7,8,9,10,11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12,13,14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899single-cell clones established from three different cell types collected from 28individuals. We identified 1,708somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.

DOI: 10.1038/s41586-023-06046-z

Source: https://www.nature.com/articles/s41586-023-06046-z

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