Modelling haemopoietic stem cell division by analysis of mutant red cells

M Vickers, G C Brown, J B Cologne, S Kyoizumi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Data describing the number of human red cells mutated at the glycophorin A locus, measured flow cytometrically, are reported for 752 adults and 49 neonates. The variance increases with age more rapidly than the approximately linear increase in mean. It is postulated that this discrepancy is explained by the known property of asymmetric stem cell division, so that the division of a single mutant stem cell may result in zero, one or two progeny stem cells. A mathematical analysis allows description of this process with three parameters: stem cell number, mean division rate and mutation rate per division. The values of these parameters can not be deduced from the data presented here. However, estimates of either stem cell number or mutation rate from other sources enable deduction of the two other parameters. The mean number of divisions per stem cell per lifetime was estimated to be about 70. This analysis therefore implies that the rate at which blood cell telomeres shorten with age acts as a direct measure of stem cell turnover. Furthermore, it is argued that this low figure implies that mutations occurring during early life, including organogenesis, are relatively important in initiating stem cell-derived malignancy. Finally, the number of human stem cell divisions per lifetime is similar to shorter-lived mammals, suggesting this number is important in the ageing process.

Original languageEnglish
Pages (from-to)54-62
Number of pages9
JournalBritish Journal of Haematology
Volume110
Publication statusPublished - 2000

Keywords

  • somatic mutation
  • haemopoietic stem cells
  • glycophorin A
  • carcinogenesis
  • ageing
  • HUMAN COLORECTAL-CARCINOMA
  • VIVO SOMATIC MUTATION
  • ATOMIC-BOMB SURVIVORS
  • GLYCOPHORIN-A LOCUS
  • ADULT BONE-MARROW
  • IN-VIVO
  • HUMAN-LYMPHOCYTES
  • CORD-BLOOD
  • ERYTHROCYTES
  • CANCER

Cite this

Modelling haemopoietic stem cell division by analysis of mutant red cells. / Vickers, M ; Brown, G C ; Cologne, J B ; Kyoizumi, S .

In: British Journal of Haematology, Vol. 110, 2000, p. 54-62.

Research output: Contribution to journalArticle

Vickers, M ; Brown, G C ; Cologne, J B ; Kyoizumi, S . / Modelling haemopoietic stem cell division by analysis of mutant red cells. In: British Journal of Haematology. 2000 ; Vol. 110. pp. 54-62.
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AB - Data describing the number of human red cells mutated at the glycophorin A locus, measured flow cytometrically, are reported for 752 adults and 49 neonates. The variance increases with age more rapidly than the approximately linear increase in mean. It is postulated that this discrepancy is explained by the known property of asymmetric stem cell division, so that the division of a single mutant stem cell may result in zero, one or two progeny stem cells. A mathematical analysis allows description of this process with three parameters: stem cell number, mean division rate and mutation rate per division. The values of these parameters can not be deduced from the data presented here. However, estimates of either stem cell number or mutation rate from other sources enable deduction of the two other parameters. The mean number of divisions per stem cell per lifetime was estimated to be about 70. This analysis therefore implies that the rate at which blood cell telomeres shorten with age acts as a direct measure of stem cell turnover. Furthermore, it is argued that this low figure implies that mutations occurring during early life, including organogenesis, are relatively important in initiating stem cell-derived malignancy. Finally, the number of human stem cell divisions per lifetime is similar to shorter-lived mammals, suggesting this number is important in the ageing process.

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