Modelling haemopoietic stem cell division by analysis of mutant red cells

Data describing the number of human red cells mutated at the glycophorin A locus, measured flow cytometrically, are reported for 752 adults and 49 neo nates. The variance increases with age more rapidly than the approximately linear increase in mean. It is postulated that this discrepancy is explaine d by the known property of asymmetric stem cell division, so that the divis ion of a single mutant stem cell may result in zero, one or two progeny ste m cells. A mathematical analysis allows description of this process with th ree parameters: stem cell number, mean division rate and mutation rate per division. The values of these parameters can not be deduced from the data p resented here. However, estimates of either stem cell number or mutation ra te from other sources enable deduction of the two other parameters. The mea n 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 telom eres shorten with age acts as a direct measure of stem cell turnover. Furth ermore, it is argued that this low figure implies that mutations occurring during early life, including organogenesis, are relatively important in ini tiating stem cell-derived malignancy. Finally, the number of human stem cel l divisions per lifetime is similar to shorter-lived mammals, suggesting th is number is important in the ageing process.