Population dynamics of normal human blood inferred from somatic mutations

TY - JOUR

T1 - Population dynamics of normal human blood inferred from somatic mutations

AU - Lee-Six, H

AU - Øbro, NF

AU - Shepherd, MS

AU - Grossmann, S

AU - Dawson, K

AU - Belmonte, M

AU - Osborne, RJ

AU - Huntly, BJP

AU - Martincorena, I

AU - Anderson, E

AU - O'Neill, L

AU - Stratton, MR

AU - Laurenti, E

AU - Green, AR

AU - Kent, DG

AU - Campbell, PJ

PY - 2018/9/27

Y1 - 2018/9/27

N2 - 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.

AB - 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.

U2 - 10.1038/s41586-018-0497-0

DO - 10.1038/s41586-018-0497-0

M3 - Article

VL - 561

SP - 473

EP - 478

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7724

ER -