The Life of A Hematopoietic Stem Cell.

<p>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 <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-Sieburg4" target="_blank">[63]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-MullerSieburg5" target="_blank">[65]</a>. 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 <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-Sieburg1" target="_blank">[8]</a>. 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 <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-MullerSieburg1" target="_blank">[2]</a>). In particular, all daughter HSCs become extinct at the same time <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-Sieburg1" target="_blank">[8]</a>. 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 <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-MullerSieburg1" target="_blank">[2]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-MullerSieburg6" target="_blank">[66]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003006#pcbi.1003006-MullerSieburg7" target="_blank">[67]</a>. Therefore, the length of time for which HSCs can repopulate an ablated host varies according to the epigenetic programs of individual HSCs.