相关实验视频
Updated: Mar 14, 2026

Characterizing Mutational Load and Clonal Composition of Human Blood
Published on: July 11, 2019
在人体成年干细胞中组织特异突变的累积
Francis Blokzijl1,2, Joep de Ligt1,2, Myrthe Jager1,2
1Center for Molecular Medicine, Cancer Genomics Netherlands, Department of Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
随着时间的推移,人类成年干细胞 (ASC) 稳步积累基因突变,导致癌症等与年龄相关的疾病. 在ASC中特定的组织突变模式可能会启动瘤的发展.
科学领域:
- 遗传学
- 分子生物学
- 癌症学
背景情况:
- 成人干细胞 (ASC) 的基因突变随着年龄的增长而积累,并与包括癌症在内的与年龄相关的疾病有关.
- 癌症风险在各个组织之间有很大差异,可能是由于ASC分裂和相关突变的数量.
研究的目的:
- 确定小肠,结肠和肝脏的正常人ASC中的全基因组突变率和模式.
- 研究ASC突变谱与癌症驱动基因突变之间的关系.
主要方法:
- 从3至87岁的人类捐赠者的初级多能ASC中获得的克隆器官培养物的测序.
- 全基因组突变模式分析和突变特征分析.
主要成果:
- 在评估的组织中,突变在ASC中稳步积累,每年大约有40种新突变.
- 与结肠和小肠ASC相比,肝脏ASC表现出不同的突变谱,归因于不同的突变过程.
- ASC突变谱与癌症驱动基因突变谱具有很高的相似性,这表明内在突变过程启动了瘤发生.
结论:
- 在ASC中的内在突变过程在启动瘤发生方面发挥着重要作用.
- 组织特异性突变模式在ASC中很早就形成,并在整个生命中保持一致.
- 尽管癌症发病率存在差异,但ASC在不同组织中以相对一致的速度积累突变.
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