The broad interests of our lab relate to the identification and characterization of tissue-specific stem cell populations in adult animals, with particular emphasis on bone marrow-derived and blood-forming (hematopoietic) stem cells and skeletal muscle progenitors. In the hematopoietic system, we are particularly interested in defining regulators of hematopoietic stem cell migration and self-renewal and are pursuing genetic, genomic, and cell biological approaches to identifying genes and gene products that control the homing, mobilization, expansion, differentiation and survival of blood-forming stem cells in normal animals and in transplant settings. In addition, we have investigated potential mechanisms and determinants of bone marrow (BM) and hematopoietic stem cell lineage plasticity, using both transplantation and parabiotic mouse models in which the origin of engrafted cells can be traced via constitutive expression of green fluorescent protein (GFP). However, while some recent data had suggested that hematopoietic stem cells (HSC) may be capable of transdifferentiation, and thereby serve as a source of regenerative cells for the repair of both blood and non-blood tissues, thus far, we have found no evidence to support a significant contribution from hematopoietic or bone marrow sources to the regeneration of non-blood tissues. Instead, we find that in the rare instances in which we can detect contributions from BM or HSC to non-hematopoietic tissues, these events generally require significant tissue injury and occur by cell fusion, not transdifferentiation. Therefore, we have initiated additional studies to identify tissue-resident stem cell populations that function robustly to regenerate damaged adult tissues, and have recently succeeded in prospectively isolating, by fluorescence activated cell sorting (FACS), a novel population of adult skeletal muscle precursor cells with robust myogenic activity. Future studies in this area will be aimed at further defining cell lineage relationships in the differentiation of muscle stem and progenitor cells, as well as at identifying signaling pathways and gene expression programs important for maintaining these muscle-resident cell populations. In addition, we will apply similar isolation strategies to other adult tissues, including cardiac muscle and pancreas, to test the hypothesis that the adult tissues harbor as yet uncharacterized, isolatable stem cell populations that may support the repair of these tissues.