Hans B Sieburg (1) and Christa E Muller-Sieburg (2)
(1) Sanford-Burnham Medical Research Institute, Department of Stem Cells and
Regenerative Medicine, 10901 North Torrey Pines Road, La Jolla CA 92037
hsieburg@sbmri.org
(2) Sanford-Burnham Medical Research Institute, Department of Stem Cells and
Regenerative Medicine, 10901 North Torrey Pines Road, La Jolla CA 92037
ABSTRACT
Stem Cells can generate whole organisms (embryonic stem cells) or complete
organ systems (adult tissue stem cells), including partially fluidic tissues
such the hematopoietic system. The power of each stem cell to (re-)generate
on this massive scale depends on the ability to give rise to all cell types by
pluri-potent (embryonic), or multi-potent (tissue) differentiation. Since differentiation
depletes their compartment, stem cells must be able to proliferate
reliably to preserve multi-potency (self-renewal). A large body of evidence collected
by us and others over the last decade for mouse and human (reviewed
in [1]), demonstrates that hematopoietic stem cells (HSCs) form a heterogeneous
population - contrasting the previous belief that all HSCs are the same.
Individual HSCs differed remarkably in their self-renewal and differentiation
behaviors when their clonal hematopoietic systems were followed in vivo over
long periods of time. The data, moreover, show that these behaviors are fixed
in the adult organism, thus suggesting that HSC heterogeneity emerges during
development. Also, we found that hematopoietic aging manifests as a shift in
the composition of the HSC compartment towards lower heterogeneity at the
system level, but unaltered capacity at the level of individual HSCs. Together,
the current data outline the long-term dynamics of hematopoiesis sufficiently to
yield unexpected mathematical and computational predictions. We argue that
reevaluating the interpretation of previous experimental and clinical findings in
light of HSC heterogeneity is an essential investment into developing improved
treatments of blood cancers in adults and the elderly.
References
[1] Christa E Muller-Sieburg, Hans B Sieburg, Jeff M Bernitz, Giulio Cattarossi
Stem cell heterogeneity: implications for aging and regenerative medicine,
Blood 119, pp. 3900–3907.
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