Characterization and quantification of clonal heterogeneity among hematopoietic stem cells: a model-based approach.

ABSTRACT: Hematopoietic stem cells (HSCs) show pronounced heterogeneity in self-renewal and differentiation behavior, which is reflected in their repopulation kinetics. Here, a single-cell-based mathematical model of HSC organization is used to examine the basis of HSC heterogeneity. Our modeling results, which are based on the analysis of limiting dilution competitive repopulation experiments in mice, demonstrate that small quantitative but clonally fixed differences of cellular properties are necessary and sufficient to account for the observed functional heterogeneity. The model predicts, and experimental data validate, that competitive pressures will amplify small clonal differences into large changes in the number of differentiated progeny. We further predict that the repertoire of HSC clones w

SUBMITTER: Roeder I 

PROVIDER: S-EPMC2597595 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature