Population dynamics of normal human blood inferred from somatic mutations.
Population dynamics of normal human blood inferred from somatic mutations.
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从体细胞突变推断出正常人血的种群动力学。
DOI：
10.1038/s41586-018-0497-0
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发表时间：
2018-09
期刊：
影响因子：
64.8
通讯作者：
Campbell PJ
中科院分区：
文献类型：
--
作者：
Lee-Six H;Øbro NF;Shepherd MS;Grossmann S;Dawson K;Belmonte M;Osborne RJ;Huntly BJP;Martincorena I;Anderson E;O'Neill L;Stratton MR;Laurenti E;Green AR;Kent DG;Campbell PJ
造血干细胞驱动血液生成，但它们的群体大小和寿命动态尚未在人类中直接量化。我们从一名59岁的正常男性的140个单细胞来源的造血干细胞和祖细胞集落中鉴定出129，582个自发的全基因组体细胞突变，并应用群体遗传学方法重建克隆动态。在系统发育树中，早期胚胎发生的细胞分裂是明显的，所有的血液都来自原肠胚形成之前的共同祖先。干细胞群体的大小在生命早期稳定增长，到青春期达到稳定的平台期。我们估计，在任何一个时间，活跃地制造白色血细胞的造血干细胞的数量在50，000 - 200，000之间。我们观察到成人造血干细胞克隆产生多系输出，包括粒细胞和B淋巴细胞。利用自然发生的突变来报告器官的克隆结构，提供了人体体细胞动力学的高分辨率重建。
Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been directly quantified in humans. We identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell–derived haematopoietic stem and progenitor colonies from a normal 59 year-old man and applied population genetics approaches to reconstruct clonal dynamics. Cell divisions from early embryogenesis were evident in the phylogenetic tree, with all blood deriving from a common ancestor that preceded gastrulation. Stem cell population size grew steadily in early life, reaching a stable plateau by adolescence. We estimate numbers of haematopoietic stem cells actively making white blood cells at any one time to be in the range 50,000-200,000. We observed adult haematopoietic stem cell clones that generate multilineage output, including granulocytes and B lymphocytes. Harnessing naturally occurring mutations to report an organ’s clonal architecture provides high-resolution reconstruction of somatic cell dynamics in humans.
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正常细胞的基因组测序揭示了发育谱系和突变过程。
影响因子：
64.8
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.
通讯作者：
Stratton, Michael R.
影响因子：
8.8
作者：
McKerrell T;Park N;Moreno T;Grove CS;Ponstingl H;Stephens J;Understanding Society Scientific Group;Crawley C;Craig J;Scott MA;Hodkinson C;Baxter J;Rad R;Forsyth DR;Quail MA;Zeggini E;Ouwehand W;Varela I;Vassiliou GS
通讯作者：
Vassiliou GS
影响因子：
64.8
作者：
Busch, Katrin;Klapproth, Kay;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
32.4
作者：
Sawai CM;Babovic S;Upadhaya S;Knapp DJHF;Lavin Y;Lau CM;Goloborodko A;Feng J;Fujisaki J;Ding L;Mirny LA;Merad M;Eaves CJ;Reizis B
通讯作者：
Reizis B
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