Population dynamics of normal human blood inferred from somatic mutations

Nature. 2018 Sep;561(7724):473-478. doi: 10.1038/s41586-018-0497-0. Epub 2018 Sep 5.

Abstract

Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been quantified directly in humans. Here we identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived haematopoietic stem and progenitor colonies from a healthy 59-year-old man and applied population-genetics approaches to reconstruct clonal dynamics. Cell divisions from early embryogenesis were evident in the phylogenetic tree; all blood cells were derived from a common ancestor that preceded gastrulation. The size of the stem cell population grew steadily in early life, reaching a stable plateau by adolescence. We estimate the numbers of haematopoietic stem cells that are actively making white blood cells at any one time to be in the range of 50,000-200,000. We observed adult haematopoietic stem cell clones that generate multilineage outputs, including granulocytes and B lymphocytes. Harnessing naturally occurring mutations to report the clonal architecture of an organ enables the high-resolution reconstruction of somatic cell dynamics in humans.

MeSH terms

  • Adult Stem Cells / cytology
  • Bayes Theorem
  • Blood Cells / cytology*
  • Blood Cells / metabolism*
  • Cell Count
  • Cell Division
  • Cell Lineage / genetics*
  • Clone Cells / cytology
  • Clone Cells / metabolism
  • DNA Mutational Analysis*
  • Embryonic Development / genetics
  • Genome, Human / genetics
  • Granulocytes / cytology
  • Granulocytes / metabolism
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Mutation*
  • Time Factors