In recent years, there has been an accumulation of data suggesting that after bone marrow transplantation, hematopoietic stem cell-derived cells can give rise to tissues of a non-hematopoietic lineage. Initial discoveries in this field led to the hypothesis that hematopoietic stem cells were capable of tissue plasticity, which went against the long held belief that tissue specific stem cells were only able to differentiate into cell lineages specific for the tissue of origin.
In our lab, we have chosen to use the musculature system as a model to study hematopoietic stem cell plasticity. Interestingly, our data suggests that hematopoietic contribution to the musculature results from macrophage fusion, rather than hematopoietic stem cell plasticity. Furthermore, we and other labs have found that the proportion of hematopoietic engrafting into muscles is highly variable depending on the marker gene used for tracking donor cells. These observations led us to directly compare hematopoietic contribution to regenerating muscle using donor cells from two different transgenic mouse strains: (1) mice that expressed the GFP gene under a β-actin promoter, and (2) mice that expressed the LacZ gene under the myosin light chain 3F promoter. When using donor cells derived from the progeny of these two mouse strains crossed, we found that all β-galactosidase positive fibers were also GFP-positive, while there were some GFP-positive fibers with no β-galactosidase expression. Since GFP is under an ubiquitous promoter while LacZ is under a muscle specific promoter, this has led us to hypothesize that the lower levels of engraftment with LacZ may be resulted from lack of nuclear reprogramming to induce fused macrophages to produce muscle specific proteins.