Show simple item record

dc.contributor.authorOsorio, Fernando G.
dc.contributor.authorHuber, Axel Rosendahl
dc.contributor.authorOka, Rurika
dc.contributor.authorVerheul, Mark
dc.contributor.authorPatel, Sachin H.
dc.contributor.authorHasaart, Karlijn
dc.contributor.authorFonteijne, Lisanne de la
dc.contributor.authorVarela Egocheaga, Ignacio 
dc.contributor.authorCamargo, Fernando D.
dc.contributor.authorBoxtel, Ruben van
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractMutation 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-cordblood- 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.es_ES
dc.description.sponsorshipThe authors would like to thank the Hartwig Medical Foundation (Amsterdam, the Netherlands) for facilitating low-input whole-genome sequencing, P.J. Coffer for providing umbilical cord blood samples, and P.J. Campbell and D.C. Wedge for sharing scripts. This study was financially supported by an EMBO long-term fellowship to F.G.O. (ALTF 655-2016), an ERC starting grant (ERC2014-STG637904) to I.V., a VIDI grant of the Netherlands Organisation for Scientific Research (NWO) (no. 016.Vidi.171.023) to R.v.B., funding from Worldwide Cancer Research (WCR) (no. 16-0193) to R.v.B., and NIH grants HL128850-01A1 and P01HL13147 to F.D.C. F.D.C. is a scholar of the Howard Hughes Medical Institute and the Leukemia and Lymphoma Society.es_ES
dc.format.extent14 p.es_ES
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationales_ES
dc.sourceCell Rep. 2018 Nov 27;25(9):2308-2316.e4es_ES
dc.subject.otherDevelopmental Lineage Treees_ES
dc.subject.otherHuman Hematopoiesises_ES
dc.subject.otherMutational Processeses_ES
dc.subject.otherSomatic Mutationses_ES
dc.titleSomatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesises_ES

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 InternationalExcept where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International