Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis.
Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis.
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DOI：
10.1016/j.celrep.2018.11.014
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发表时间：
2018-11-27
期刊：
影响因子：
8.8
通讯作者：
van Boxtel R
中科院分区：
文献类型：
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作者：
Osorio FG;Rosendahl Huber A;Oka R;Verheul M;Patel SH;Hasaart K;de la Fonteijne L;Varela I;Camargo FD;van Boxtel R
Mutation accumulation during life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Somatic mutations in blood progenitors can provide insight into the rate and processes underlying this accumulation, as well as the developmental lineage tree and stem cell division numbers. Here, we catalog mutations in the genomes of human-bone-marrow-derived and umbilical-cord-blood-derived hematopoietic stem and progenitor cells (HSPCs). We find that mutations accumulate gradually during life with approximately 14 base substitutions per year. The majority of mutations were acquired after birth and could be explained by the constant activity of various endogenous mutagenic processes, which also explains the mutation load in acute myeloid leukemia (AML). Using these mutations, we construct a developmental lineage tree of human hematopoiesis, revealing a polyclonal architecture and providing evidence that developmental clones exhibit multipotency. Our approach highlights features of human native hematopoiesis and its implications for leukemogenesis. Base substitution rate is similar among human HSCs and MPPs Mutations accumulate with 14 mutations per year per cell Three signatures explain mutation spectra in HSC/MPPs and are also present in AML Shared mutations allow construction of a developmental lineage tree Osorio et al. report lifelong mutation accumulation in human hematopoietic stem and progenitor cells, which is explained by three distinct mutational signatures. Shared somatic mutations between cells of the same donor enable the construction of a developmental lineage tree and quantification of each branch to mature blood cell populations.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
12.3
作者：
Blokzijl F;Janssen R;van Boxtel R;Cuppen E
通讯作者：
Cuppen E
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.
DOI：
10.1126/science.aao4426
发表时间：
2018-02-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lodato MA;Rodin RE;Bohrson CL;Coulter ME;Barton AR;Kwon M;Sherman MA;Vitzthum CM;Luquette LJ;Yandava CN;Yang P;Chittenden TW;Hatem NE;Ryu SC;Woodworth MB;Park PJ;Walsh CA
通讯作者：
Walsh CA
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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