Stem cells, hematopoiesis, and osteogenesis in the bone marrow
Sean J. Morrison
Howard Hughes Medical Institute and Children’s Research Institute at the University of Texas Southwestern Medical Center
The bone marrow contains two physiologically important types of stem cells that must persist throughout life: hematopoietic stem cells (HSCs) that maintain the blood and immune systems and skeletal (mesenchymal) stem cells that maintain the skeleton. HSCs reside in specialized microenvironments, or niches, in the bone marrow that promote HSC maintenance and regulate HSC function. Work over the past 20 years in the Morrison lab identified the HSC niche and the skeletal stem cells in adult bone marrow. In particular, the Morrison lab identified Leptin Receptor+ (LepR+) stromal cells in adult bone marrow that are the main source of growth factors, including Stem Cell Factor, that are required for the maintenance of HSCs and early restricted hematopoietic progenitors. In addition being a critical source of growth factors, LepR+ cells include skeletal stem cells, osteogenic, and adipogenic progenitors that give rise to all of the osteoblasts and adipocytes that form in adult bone marrow. These LepR+ cells play a critical role in the maintenance and repair of the adult skeleton. In a series of studies over the past 10 years, the Morrison lab has discovered several new mechanisms by which LepR+ cells regulate the production of new blood and bone cells.