Role of telomerase in hematopoietic stem cells.

Studies in hematopoietic stem cell (HSC) biology are often focused on "self-renewal" and differentiation. Implicit in the word self-renewal is that the two daughter cells generated by a self-renewal division are identical to the parental cell. Strictly speaking, this is not possible because DNA is continuously damaged and repaired by DNA-repair mechanisms that are not 100% efficient. It is important to note that the efficiency of DNA repair varies greatly among different stem cell types. For example, embryonic stem cells are quite resistant to DNA damage and maintain the length of telomere repeats on serial passage, whereas HSCs are quite sensitive to DNA damage and less able to maintain telomere length. Most likely, differences between stem cell types in DNA repair and telomere maintenance pathways coevolved with cell mass, turnover, reproductive strategy, and life span. This idea has given rise to the notion that many aspects of normal aging could primarily reflect limitations in DNA repair and telomere-maintenance pathways in the (stem) cells of the soma. In humans, levels of telomerase in HSCs are under extremely tight control, as is illustrated by the marrow failure in patients with (mild) telomerase deficiencies. Here, the role of telomerase in human HSC biology is reviewed, and it is proposed that telomerase has an important role in the repair of G-rich DNA.