Lifespan Differences in Hematopoietic Stem Cells are Due to Imperfect Repair and Unstable Mean-Reversion
Figure 2
The Life of A Hematopoietic Stem Cell.
A: Limited lifespan: When a monoclonal hematopoietic system is initiated by transplanting a single HSC (dark blue sphere), it expands to a pool of clonal HSCs through self-renewal (cluster of blue spheres). This pool distributes through the organism. HSCs differentiate to generate mature cells of all lineages (shown as magenta, orange, green, light-blue spheres). This process depends on the intrinsic properties of the founder HSC [63], [65]. The overall output of mature cells in blood (measured in %-donor type cells; vertical axis (not shown in the figure)) over time (horizontal axis labelled “Lifespan”) is indicated by the black curve. For all normal HSCs, this kinetic has a ballistic shape, thus indicating that a clone's ability to produce mature cells of all major lineages (the lifespan) is limited. The lifespan is mathematically predictable with high accuracy from few initial points of the repopulation kinetic [8]. B: Programmed Lifespan: When daughter HSCs derived from a single ancestral HSC are transplanted into separate hosts, the repopulation kinetics are very similar (modified from [2]). In particular, all daughter HSCs become extinct at the same time [8]. This suggested that the lifespan is epigenetically fixed (programmed) and heritable in self-renewal. C: Lifespan Diversity: The relialogram illustrates that when HSCs are sampled from bone marrow, lifespans of different durations are found [2], [66], [67]. Therefore, the length of time for which HSCs can repopulate an ablated host varies according to the epigenetic programs of individual HSCs.