The human skeleton is renewed and regenerated throughout life, by a cellular process known as bone remodeling. Stem cells are clono-genic cells that are capable of differentiation into multiple mature cell types (multipotency), and simultaneously replenishing stem cell pool (self-renewal), which allows them to sustain tissue development and maintenance. Circulating mesenchymal stromal/stem cells (MSCs), are mobile adult stem cells with specific gene expression profiling, as well as enhanced mitochondrial remodeling as a promising source for personalized cell and gene therapy. A global LGR5-associated genetic interaction network highlights the functional organization and molecular phenotype of circulating MSCs.