The Fetal-to-Adult Hematopoietic Stem Cell Transition and its Role in Childhood Hematopoietic Malignancies

As with most organ systems that undergo continuous generation and maturation during the transition from fetal to adult life, the hematopoietic and immune systems also experience dynamic changes. Such changes lead to many unique features in blood cell function and immune responses in early childhood. The blood cells and immune cells in neonates are a mixture of fetal and adult origin due to the co-existence of both fetal and adult types of hematopoietic stem cells (HSCs) and progenitor cells (HPCs). Fetal blood and immune cells gradually diminish during maturation of the infant and are almost completely replaced by adult types of cells by 3 to 4 weeks after birth in mice. Such features in early childhood are associated with unique features of hematopoietic and immune diseases, such as leukemia, at these developmental stages. Therefore, understanding the cellular and molecular mechanisms by which hematopoietic and immune changes occur throughout ontogeny will provide useful information for the study and treatment of pediatric blood and immune diseases. In this review, we summarize the most recent studies on hematopoietic initiation during early embryonic development, the expansion of both fetal and adult types of HSCs and HPCs in the fetal liver and fetal bone marrow stages, and the shift from fetal to adult hematopoiesis/immunity during neonatal/infant development. We also discuss the contributions of fetal types of HSCs/HPCs to childhood leukemias.