Cho RH, Sieburg HB, Muller-Sieburg CE.. A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 111: 5553-5561

Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Blood (Impact Factor: 10.45). 07/2008; 111(12):5553-61. DOI: 10.1182/blood-2007-11-123547
Source: PubMed


Whether hematopoietic stem cells (HSCs) change with aging has been controversial. Previously, we showed that the HSC compartment in young mice consists of distinct subsets, each with predetermined self-renewal and differentiation behavior. Three classes of HSCs can be distinguished based on their differentiation programs: lymphoid biased, balanced, and myeloid biased. We now show that aging causes a marked shift in the representation of these HSC subsets. A clonal analysis of repopulating HSCs demonstrates that lymphoid-biased HSCs are lost and long-lived myeloid-biased HSCs accumulate in the aged. Myeloid-biased HSCs from young and aged sources behave similarly in all aspects tested. This indicates that aging does not change individual HSCs. Rather, aging changes the clonal composition of the HSC compartment. We show further that genetic factors contribute to the age-related changes of the HSC subsets. In comparison with B6 mice, aged D2 mice show a more pronounced shift toward myeloid-biased HSCs with a corresponding reduction in the number of both T- and B-cell precursors. This suggests that low levels of lymphocytes in the blood can be a marker for HSC aging. The loss of lymphoid-biased HSCs may contribute to the impaired immune response to infectious diseases and cancers in the aged.

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    • "Fasting Inhibits IGF-1/PKA to Promote Regeneration myeloid-biased, and balanced-HSCs ratio (Figures 2F, S2D, and S2E). Whereas most HSCs from young mice are balanced in lymphopoiesis and myelopoiesis, the majority of HSCs from elderly mice are myeloid biased (Beerman et al., 2010; Challen et al., 2010; Cho et al., 2008; Dykstra et al., 2007; Morita et al., 2010; Muller-Sieburg et al., 2004; Pang et al., 2011). We therefore investigated if PF cycles can correct this bias in aged mice. "
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    • "However, our data cannot disentangle cell-type effects. Other contributing factors may include developmental processes such as age-related changes to the progenitor cell pool [75-77], as suggested previously [28], or age-related shifts in blood cell signaling and metabolism [78]. "
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    Genome Medicine 10/2013; 5(10):96. DOI:10.1186/gm500 · 5.34 Impact Factor
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    • "As mentioned above, stem cells in general are defined by their ability to self-renew and give rise to differentiated progenies. The neural stem cells (NSCs) in the adult brain have not yet been proven to be bona fide stem cells, since there is an apparent heterogeneity in the cell populations at multiple stages of adult neurogenesis (Lugert et al. 2010; Cho et al. 2008; Conboy and Rando 2005; Decarolis et al. 2013). The two main regions in the adult brain that give rise to new neurons are the subventricular zone (SVZ) lining the lateral ventricles and the subgranular layer (SGL) of the hippocampal dentate gyrus (Fuentealba et al. 2012). "
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