Does telomere shortening limit the replicative capacity of hematopoietic stem cells?
Hematopoietic stem cells can only be serially transplanted 5-7 times in mice, indicating that HSC have a finite replicative capacity (Harrison et al., 1978; Harrison and Astle, 1982). However, HSC also undergo continuous self-renewal and differentiation to provide a continuous supply of hematopoietic cells throughout the organismal lifespan (Cheshier et al., 1999), and therefore must have a substantial replicative capacity. In bone marrow or HSC transplant recipients, the continuous and prompt supply of blood cells post-transplant is essential, thus the question as to whether telomere shortening limits the replicative capacity of HSC is of general clinical interest. A number of studies have demonstrated that telomeres do shorten during replicative aging of HSC. First, telomere length was found to be shorter for candidate HSC from the marrow of two adult donors compared to candidate HSC from fetal cord blood (Vaziri et al., 1994). Second, an accelerated decrease in telomere length has b
