Ontogenic growth of the haemopoietic stem cell pool in humans

Abstract

Recently, the size of the active stem cell pool has been predicted to scale allometrically with the adult mass of mammalian species with a 3/4 power exponent, similar to what has been found to occur for the resting metabolic rate across species. Here we investigate the allometric scaling of human haemopoietic stem cells (HSCs) during ontogenic growth and predict a linear scaling with body mass. We also investigate the allometric scaling of resting metabolic rate during growth in humans and find a linear scaling with mass similar to that of the haemopoietic stem cell pool. Our findings suggest a common underlying organizational principle determining the linear scaling of both the stem cell pool and resting metabolic rate with mass during ontogenic growth within the human species, combined with a 3/4 scaling with adult mass across mammalian species. It is possible that such common principles remain valid for haemopoiesis in other mammalian species.

Figure 1

Scaling of the mean reticulocyte count (R_TD) with body mass during ontogenic growth in humans. Data for girls are shown with open circles, whereas data for boys are shown with solid circles. The scaling of R_TD with mass is well approximated (in both cases, correlation coefficient is greater than 0.999) by a linear relation (straight dashed and solid lines, respectively), as opposed to a 3/4 scaling, illustrated by the curved lines (dashed and solid lines, respectively). Such an intra-species allometric relation with exponent 1 contrasts with the allometric exponent 3/4 obtained for inter-species scaling for mammals spanning a mass range of five orders of magnitude.

Figure 2

Ontogenic growth model for humans. Experimental data are represented with open circles for girls and solid circles for boys. (a) Experimental data for age dependence of mass. Solid and dashed lines correspond to polynomial fits to data and illustrate the quality of fit. (b) We test the assumption of West et al. of extrapolating to intra-specific resting metabolic rate during growth the 3/4 scaling obtained for inter-specific data. Clearly, this assumption is unable to account simultaneously for the low and high regimes of B(t). The Χ² values for boys and girls are 55.4 and 30.4, respectively. (c) Introducing data from (a) (and their time derivatives) in equation (1.2) leads to the age-dependent solution for B(t) depicted with solid and dashed lines. Comparison with experimental data shows that these solutions of equation (1.2) account better for the overall age dependence of B(t), supported by the associated Χ² values for boys and girls, which now become 21.6 and 9.8, respectively. A nonlinear least squares fit to these lines leads to nearly linear scaling exponents (b=0.98) for the rest metabolic rate as a function of mass during growth (+ and ×), in agreement with our prediction for the mass scaling of the active stem cell pool.