Somatic mutations reveal lineage relationships and age-related mutagenesis in human hematopoiesis
Mutation accumulation during human 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 catalogue somatic mutations in the genomes of human bone marrow-derived and cord blood-derived hematopoietic stem and multipotent progenitor cells (HSPCs) and find that base substitutions accumulate with approximately 17 base substitutions per year in both populations, while insertions and deletions occur sporadically and at low numbers. The majority of mutations in adult HSPCs were acquired after birth and could be explained by the constant activity of various endogenous processes, which also explains the mutation load in acute myeloid leukemia (AML). We construct a developmental lineage tree revealing a polyclonal architecture of the hematopoietic progenitor compartment and providing evidence that developmental clones exhibit multipotency, though lineage biases can be detected. Our approach highlights novel features of human native hematopoiesis and its implications for leukemogenesis.
- Type: Other
- Archiver: EGA European Genome-Phenome Archive
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|EGAD00001004451||HiSeq X Ten||30|
Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis.
Cell Rep 25: 2018 2308-2316.e4
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