Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis

• DOI: 10.1016/j.celrep.2018.11.014
• Publication Date: 2018-11-27T10:37:47Z
• Authors: Fernando G. Osorio; Axel Rosendahl Huber; Rurika Oka; Mark Verheul; Sachin H. Patel; Karlijn Hasaart; Lisanne de la Fon...; Ignacio Varela; Fernando D. Camargo; Ruben van Boxtel
• Keywords: Lineage (genetic); Hematopoietic stem cell

Mutation accumulation during life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Somatic mutations in blood progenitors provide insight into rate and processes this accumulation, as well developmental lineage tree stem cell division numbers. Here, we catalog genomes of human-bone-marrow-derived umbilical-cord-blood-derived progenitor cells (HSPCs). We find that accumulate gradually with approximately 14 base substitutions per year. The majority were acquired after birth could be explained by constant activity various endogenous mutagenic processes, which also explains mutation load acute myeloid leukemia (AML). Using these mutations, construct a human hematopoiesis, revealing polyclonal architecture providing evidence clones exhibit multipotency. Our approach highlights features native hematopoiesis its implications for leukemogenesis.