在正常结直肠表皮中广泛的体质L1逆转换
Chang Hyun Nam1, Jeonghwan Youk1,2,3, Jeong Yeon Kim2
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Nature
|May 10, 2023
概括
体细胞通过长间隔的核元素-1 (L1) 逆转换,一个移动元素来积累基因组变化. 这项研究揭示了正常细胞中的L1活性,随着年龄的增长和结直肠癌的增加.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 基因组变化会在整个生命中积累在体细胞中.
- 在正常细胞突变场景中,长间隔核元素-1 (L1) 逆转换的作用尚不清楚.
研究的目的:
- 研究单细胞克隆的全基因组序列,以了解正常细胞中的体质L1逆转换.
- 确定不同细胞类型和年龄的L1逆转换事件的速率,特征和调节.
主要方法:
- 来自28个人的899个单细胞克隆的全基因组测序.
- 鉴定和分析体质L1逆转移事件.
- 源L1元素的指纹和反转换活动的多维分析.
主要成果:
- 确定了1708个体质L1逆转移事件,在结直肠上皮层中丰富,与年龄相关.
- 从早期的胚胎发生体内L1逆转换,在器官生成过程中建立了表观遗传调节.
- 具有较低等位基因频率的L1s表现出更高的活性,只有L1转录的一小部分被逆转移.
结论:
- 在人类一生中,体内L1逆转换有助于正常细胞的马赛克.
- 在结直肠瘤发生过程中,L1逆转移率显著增加.
- 这项研究提供了可转移元素的基因组和表观基因组调节的见解.
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