Population dynamics of normal human blood inferred from somatic mutations

Henry Lee-Six, Nina Friesgaard Øbro, Mairi S. Shepherd, Sebastian Grossmann, Kevin Dawson, Miriam Belmonte, Robert J. Osborne, Brian J. P. Huntly, Inigo Martincorena, Elizabeth Anderson, Laura O’Neill, Michael R. Stratton, Elisa Laurenti, Anthony R. Green (), David G. Kent () and Peter J. Campbell ()
Additional contact information
Henry Lee-Six: Cancer Genome Project, Wellcome Trust Sanger Institute
Nina Friesgaard Øbro: University of Cambridge
Mairi S. Shepherd: University of Cambridge
Sebastian Grossmann: Cancer Genome Project, Wellcome Trust Sanger Institute
Kevin Dawson: Cancer Genome Project, Wellcome Trust Sanger Institute
Miriam Belmonte: University of Cambridge
Robert J. Osborne: Cancer Genome Project, Wellcome Trust Sanger Institute
Brian J. P. Huntly: University of Cambridge
Inigo Martincorena: Cancer Genome Project, Wellcome Trust Sanger Institute
Elizabeth Anderson: Cancer Genome Project, Wellcome Trust Sanger Institute
Laura O’Neill: Cancer Genome Project, Wellcome Trust Sanger Institute
Michael R. Stratton: Cancer Genome Project, Wellcome Trust Sanger Institute
Elisa Laurenti: University of Cambridge
Anthony R. Green: University of Cambridge
David G. Kent: University of Cambridge
Peter J. Campbell: Cancer Genome Project, Wellcome Trust Sanger Institute

Nature, 2018, vol. 561, issue 7724, 473-478

Abstract: 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.

Keywords: Stem Cells; Haematopoietic Stem Cell; Allele Fraction; Molecular Time; Clonal Contributions (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0497-0

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