Hematopoietic Stem Cells

Hematopoietic stem cells were postulated to exist over 100 years ago. Experimental verification of their existence in mice was provided by Drs. James Till and Ernest McCulloch in 1961, and the clinical use of HSCs was pioneered by E. Donnall Thomas in the late 1960s. In addition to their role in the cure of a variety of malignancies, severe autoimmune disorders, and states of marrow failure, experimental study of HSCs have served as the road map for our understanding of stem cell development in all of mammalian biology. The transcription factors and growth promoting cytokines required for stem cell self renewal and expansion were first identified in HSCs. The notion of stem cell trafficking and migration and the molecular bases for these properties were first determined for HSCs. And the concept of a nurturing microenvironment that provides critical survival and quiescence signals, and governs the total body levels of stem cells has been best evaluated for the marrow stem cell niche. The 2008 ASH Presidential Symposium will bring together three eminent biomedical scientists who have made landmark contributions to our understanding of hematopoietic stem cell biology. Dr. Stuart Orkin will discuss the molecular determinants of “stem-ness,” the properties that allow for self-renewal and expansion, and that govern the fate of stem cells once they begin to differentiate into the formed elements of the blood. Dr. Amy Wagers will then discuss the cellular and molecular bases for stem cell migration, comparing the process for HSCs with that of other organs. Finally, Dr. Francoise Dieterlen-Lièvre will discuss the HSC niche, focusing our attention on the cellular anatomy, the changing sites of hematopoiesis during development, and the cell surface molecules and soluble growth factors that contribute to the HSC survival, proliferation, and differentiation.