Stem cell biology is a promising, fast-growing field that aims to develop cell-based tools for the treatment of a wide range of diseases. Special attention is paid to bone marrow cells that play a role in the musculoskeletal system. Bone marrow contains hematopoietic stem cells (HSCs) and stromal cells that form the reticular network that supports HSCs formation. Stromal cells also contain mesenchymal stem cells (MSCs) that differentiate to various lineages. The major obstacles in utilizing stem cells are identifying these cells and following the signaling pathways that control the cells ’ fate. The interactions of stem cells with an extracellular matrix and other cells create a tissue-specific niche that is responsible for regulating cell differentiation. It is important to identify biomarkers that will enable the isolation, selection and expansion of stem cells in vitro to allow their use for cell therapy. The study of stem cells differentiation is based on various techniques, including the generation of antibodies to specific cellular sub-populations and high throughput analysis at transcriptome and proteome levels. Advances in transcriptome and proteome profiling will establish the molecular signature and will allow the discovery of the cell type specific differentiation programming. Such analysis identified several proteins related to chromatin remodeling factors, cell adhesion molecules and extracellular matrix ligands that localize cells at the specific niche. Detailed interpretation of the transcriptional and translational expression patterns will provide understanding of key properties of MSCs and allow their future use in regenerative medicine.