A new study by Gerald de Haan, Leonid Bystrykh, and colleagues suggests that the skeletal distribution of transplanted hematopoietic stem cell (HSC) clones is surprisingly nonuniform.
The extent to which HSCs engraft in different bones and subsequently move between bone marrow niches is poorly understood. Much of what we do know comes from experiments using parabiotic rodents with shared circulation. These and other studies suggest that HSCs egress continuously from their niche into the circulation. Under these conditions, one would expect individual HSC clones to eventually be represented equally in all bones of the body. This new study, however, suggests that some transplanted HSC clones preferentially expand in certain skeletal sites with limited migration to others. Other clones were more indiscriminant.
Using viral barcoding to monitor transplanted mouse HSC clones, Verovskaya et al. uncovered a highly skewed representation within different bones up to 11 months posttransplantation. Clonal differences were observed with both young and old HSCs and were maintained when clones from particular bones were transplanted into secondary recipients. Strikingly, just a single treatment with G-CSF equilibrated the skeletal distribution of all clones.
This work has significant implications for both clinical practice and experimental research. It may be important, for example, to take marrow biopsies from more than one site (rather than a single site as is the current practice) to fully assess hematopoietic clonality after transplantation. This issue should also be addressed in future mouse barcoding studies, as the routine practice of using one limb for secondary transplants might exclude clones that preferentially reside in other skeletal sites.
In the long term, this paper should provide the groundwork for mechanistic studies addressing why HSCs expand in some skeletal sites and not others, how G-CSF treatment leads to rapid clonal redistribution, and what role preconditioning irradiation might play in these processes.