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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

ABSTRACT

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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    • "Single cell based analysis shows DNA damage accumulation and myeloid lineage bias in aged HSCs (Walter et al., 2015). Nevertheless, counter opinion maintains that these observations could be the result of selective expansion of myeloid biased HSCs and loss of HSCs with lymphoid potential (Cho et al., 2008). No apparent differences between the myeloid biased HSCs from young and old mice were reported. "
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