Aging of Hematopoietic Stem Cells

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The self-renewal capacity of all types of stem cells should assure that these cells are maintained throughout life and prevent exhaustion of the stem cell pools. Indeed, when populations of hematopoietic stem cells (HSC) were serially transferred it became clear that HSC can function much longer than the life-span of the animal,. However, HSC show extensive heterogeneity in their self-renewal capacity. For example, there is a strong genetic component to the aging of HSC. Even within the HSC compartment of a single animal, considerable heterogeneity of the self-renewal capacity of individual HSC can be demonstrated. It was thought that HSC heterogeneity derives from stochastic HSC behavior. However, our clonal analysis of HSC indicates that many aspects of HSC behavior, including self-renewal capacity, are epigenetically pre-programmed. For example, we identified a subpopulation of HSC, called myeloid-biased (My-bi) HSC that contribute much longer to peripheral hematopoiesis than other types of HSC. We are currently exploring the hypothesis that aging of the HSC compartment is caused by the depletion of short-lived HSC. The aged behavior of HSC could then be explained by the distinct function of long-lived My-bi HSC rather then a change in the behavior of all HSC.

Hematopoietic Stem Cells

Lineage-biased Stem Cells Detected in Clonal Analysis

Aging of Hematopoietic Stem Cells

Markers for Hematopoietic Stem Cells

Genes that Control the Size of the Stem Cell Compartment