Counting divisions in a human somatic cell tree -: How, what and why?
Counting divisions in a human somatic cell tree -: How, what and why?
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DOI：
10.4161/cc.5.6.2570
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发表时间：
2006-03-16
期刊：
影响因子：
4.3
通讯作者：
Tavaré, S
中科院分区：
文献类型：
--
作者：
Shibata, D;Tavaré, S
一个人体内的数十亿个细胞可以通过谱系组织成一个单一的体细胞树，从受精卵开始，到现在的细胞结束。从理论上讲，这棵树可以从复制错误中重建出来，这些错误秘密地记录了分裂和祖先。这种分子钟方法目前是不切实际的，因为体细胞突变是罕见的，但通过替代表观遗传修饰的5'至3'顺序如CpG甲基化，更可行的测量是可能的。表观遗传体细胞错误很容易被检测为与年龄相关的甲基化变化，这表明某些成体干细胞经常分裂并在小生境中“竞争”生存。任何人类细胞的谱系都有可能被重建，而无需事先的实验操作，只需阅读记录在其基因组中的历史。
The billions of cells within an individual can be organized by genealogy into a single somatic cell tree that starts from the zygote and ends with present day cells. In theory, this tree can be reconstructed from replication errors that surreptitiously record divisions and ancestry. Such a molecular clock approach is currently impractical because somatic mutations are rare, but more feasible measurements are possible by substituting instead the 5' to 3' order of epigenetic modifications such as CpG methylation. Epigenetic somatic errors are readily detected as age-related changes in methylation, which suggests certain adult stem cells divide frequently and "compete" for survival within niches. Potentially the genealogy of any human cell may be reconstructed without prior experimental manipulation by merely reading histories recorded in their genomes.