Population dynamics of normal human blood inferred from somatic mutations
Open accessAbstract
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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Time-dependent accumulation of stochastic DNA damage hampers stem cell functionality, increases mutations during human HSC ageing, impairs functional properties, promotes clonal expansion and loss of clonal diversity, and raises oncogenic potential.
“Thus, time-dependent accumulation of stochastic DNA damage severely hampers stem cell functionality, increasing mutations during human HSC ageing80, impairing functional properties, promoting clonal expansion of positively selected somatic mutations resulting in loss of clonal diversity81 or raising the potential for oncogenic transformation.”
From The central role of DNA damage in the ageing process (2021) · cites this paper as [80]
Humans have 50,000 to 200,000 hematopoietic stem cells (HSCs).
“It is estimated that humans have 50,000 to 200,000 hematopoietic stem cells (HSCs) 13.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [13]
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- Authors
- Lee-Six, H., Øbro, N. F., Shepherd, M. S., Grossmann, S., Dawson, K., Belmonte, M., Osborne, R. J., Huntly, B. J. P., Martincorena, I., Anderson, E., O’Neill, L., Stratton, M. R., Laurenti, E., Green, A. R., Kent, D. G., & Campbell, P. J.
- Affiliations
- Wellcome Sanger Institute (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Corresponding author
- Green, Anthony R.
- Kent, David G.
- Campbell, Peter J.
- ORCID
- Venue
- Nature
- Published
- 2018-09
- Volume
- 561
- Issue
- 7724
- Pages
- 473-478
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6163040
- OpenAlex
- W2889734305
- Cited by
- 604
- References
- 36
- Citations by year
- 2026: 33 · 2025: 78 · 2024: 81 · 2023: 76 · 2022: 89 · 2021: 96 · 2020: 86 · 2019: 58 · 2018: 7
- FWCI
- 44.29
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- European Hematology Association
- Leukemia and Lymphoma Research
- Wellcome Trust (103858/Z/14/Z, 107630/Z/15/Z, WT088340MA)
- Cancer Research UK (21762, 25508, 21777)
- Lundbeckfonden (R210-2015-2686)
- Blood Cancer UK (15008)
- Medical Research Council (MR/M008975/1, MC_PC_12009, MR/M010392/1, MR/R009708/1, MC_PC_16040)
- Biotechnology and Biological Sciences Research Council (1800757)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- hematopoietic stem cells, somatic mutations, clonal dynamics, hematopoiesis, phylogenetic inference, embryonic cell division, B cells, granulocytes, myeloid cells, human blood
- MeSH terms
- Bayes Theorem, Blood Cells, Cell Count, Cell Division, Clone Cells, DNA Mutational Analysis, Granulocytes, Hematopoiesis, Hematopoietic Stem Cells, Humans, Lymphocytes, Male, Middle Aged, Mutation, Time Factors, Genome, Human, Cell Lineage, Embryonic Development, Adult Stem Cells
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