Genome sequencing of normal cells reveals developmental lineages and mutational processes.
Genome sequencing of normal cells reveals developmental lineages and mutational processes.
复制标题
正常细胞的基因组测序揭示了发育谱系和突变过程。
DOI：
10.1038/nature13448
复制
发表时间：
2014-09-18
期刊：
影响因子：
64.8
通讯作者：
Stratton, Michael R.
中科院分区：
文献类型：
--
作者：
Behjati, Sam;Huch, Meritxell;van Boxtel, Ruben;Karthaus, Wouter;Wedge, David C.;Tamuri, Asif U.;Martincorena, Inigo;Petljak, Mia;Alexandrov, Ludmil B.;Gundem, Gunes;Tarpey, Patrick S.;Roerink, Sophie;Blokker, Joyce;Maddison, Mark;Mudie, Laura;Robinson, Ben;Nik-Zainal, Serena;Campbell, Peter;Goldman, Nick;van de Wetering, Marc;Cuppen, Edwin;Clevers, Hans;Stratton, Michael R.
存在于细胞基因组中的体细胞突变已经在多细胞生物体的一生中积累。这些突变可以提供对发育谱系树的见解，每个细胞经历的分裂次数以及已经运作的突变过程。在这里，我们对来自健康小鼠多个组织的克隆系进行了全基因组测序。使用体细胞碱基替换，我们重建了每只动物的早期细胞分裂，证明了胚胎细胞对成体组织的贡献。在每个细胞积累的突变数量和类型方面观察到组织之间的差异，这可能反映了它们经历的细胞分裂数量的差异以及不同突变过程的不同贡献。如果体细胞突变率与小鼠相似，则结果表明可以精确了解正常人类细胞的发育和诱变。
The somatic mutations present in the genome of a cell have been accumulated over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree, the number of divisions each cell has undergone and the mutational processes that have been operative. Here, we conducted whole genome sequencing of clonal lines derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.
登录
查看更多内容
影响因子：
48
作者：
Carlson, Cheryl A.;Kas, Arnold;Kirkwood, Robert;Hays, Laura E.;Preston, Bradley D.;Salipante, Stephen J.;Horwitz, Marshall S.
通讯作者：
Horwitz, Marshall S.
影响因子：
4.4
作者：
Zhou W;Tan Y;Anderson DJ;Crist EM;Ruohola-Baker H;Salipante SJ;Horwitz MS
通讯作者：
Horwitz MS
影响因子：
11.4
作者：
Schepers, Arnout G.;Vries, Robert;Clevers, Hans
通讯作者：
Clevers, Hans
DOI：
10.1073/pnas.0601265103
发表时间：
2006-04-04
影响因子：
11.1
作者：
Salipante, SJ;Horwitz, MS
通讯作者：
Horwitz, MS
影响因子：
64.5
作者：
Nik-Zainal S;Van Loo P;Wedge DC;Alexandrov LB;Greenman CD;Lau KW;Raine K;Jones D;Marshall J;Ramakrishna M;Shlien A;Cooke SL;Hinton J;Menzies A;Stebbings LA;Leroy C;Jia M;Rance R;Mudie LJ;Gamble SJ;Stephens PJ;McLaren S;Tarpey PS;Papaemmanuil E;Davies HR;Varela I;McBride DJ;Bignell GR;Leung K;Butler AP;Teague JW;Martin S;Jönsson G;Mariani O;Boyault S;Miron P;Fatima A;Langerød A;Aparicio SA;Tutt A;Sieuwerts AM;Borg Å;Thomas G;Salomon AV;Richardson AL;Børresen-Dale AL;Futreal PA;Stratton MR;Campbell PJ;Breast Cancer Working Group of the International Cancer Genome Consortium
通讯作者：
Breast Cancer Working Group of the International Cancer Genome Consortium