Journal
NATURE
Volume 561, Issue 7724, Pages 473-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-018-0497-0
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Funding
- Leukemia Lymphoma Society
- WBH Foundation
- Wellcome Trust
- Wellcome Trust PhD studentship
- Danish Lundbeck Fellowship (2016-17)
- BBSRC CASE Industrial PhD Studentship
- Bloodwise Bennett Fellowship [15008]
- European Research Council [ERC-2016-STG-715371]
- European Hematology Association Non-Clinical Advanced Research Fellowship
- Bloodwise
- Cancer Research UK
- Kay Kendall Leukaemia Fund
- Leukemia and Lymphoma Society of America
- Wellcome Trust Sir Henry Dale Fellowship
- BBSRC
- European Haematology Association NonClinical Advanced Research Fellowship
- Medical Research Council
- BBSRC [1800757] Funding Source: UKRI
- MRC [MR/M010392/1, MR/M008975/1, MR/S036113/1, MR/R009708/1, MC_PC_16040] Funding Source: UKRI
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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.
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