Regulation of Blood Stem Cell Development

Understanding how the blood system is formed is an ongoing fundamental research challenge. Developmental biology has provided many insights into the molecules and processes that affect the formation of the blood tissues, both in health and disease. It is of particular interest for clinical transplantation therapies to understand how hematopoietic stem cells (HSCs)-the self-renewing purveyors of the adult blood system that produce over 10 different functionally specialized cell lineages and over 10(11) cells daily-are generated during embryonic stages. Recent successes to reprogram the fate of adult differentiated cells to pluripotency and to other cell lineages now highlight the importance of identifying the cells and molecules that affect the in vivo developmental initiation of rare and robust transplantable HSCs. The close association of the developing hematopoietic and vascular system, hematopoietic cell mobility through the circulation, and the essential role of the embryonic hematopoietic system in adult hematopoietic cell development make this a formidable study. This chapter reviews the advances, controversies, and current state of our knowledge of the growing field of hematopoietic development, with a special focus on the regulation of the natural transdifferentiation of endothelial cells to HSCs within the developing embryo.