For many adult skeletal stem cell populations, we lack the ability to identify them in complex tissue environments and determine whether they contribute to the repair of skeletal tissue. The inability to study adult stem cells within their natural environment is a critical barrier that must be overcome in order to advance our understanding of how they contribute to regenerative processes. Here we focus on bone marrow derived mesenchymal stem cells (BMSCs), an adult stem cell population with great therapeutic potential. Genetic approaches in mice can be used that would allow us to identify and fate map BMSCs in bone. Recent developments in our work have identified a new transgenic reporter gene animal model that identifies BMSCs in bone marrow. The objectives of this proposal will continue the characterization of this animal model to confirm our preliminary studies and establish an inducible Cre version that will allow us to fate map this cell population in vivo. Collectively, these animal models will allow us to assay the number of BMSCs present in the bone marrow and determine their contribution over time to skeletal repair. PUBLIC HEALTH RELEVANCE: Bone marrow derived mesenchymal stem cells (BMSCs) are an intensively studied adult stem cell population that retain the ability to differentiate into different skeletal cell types. Therefore, BMSCs have great therapeutic value for skeletal tissue repair. The goal of this proposal focuses on establishing animal models that would allow for the accurate identification of BMSCs in bone tissue and determining their contribution to skeletal repair.