Defining Adult Stem Cell Function at Its Simplest: The Ability to Replace Lost Cells through Mitosis

Classic studies on hematopoiesis indicate that blood cell numbers are maintained by rare, hard-wired, transplantable stem cells (SCs). Subsequent studies in other organs have implicitly assumed that all SC hierarchies follow the design of the hematopoietic system. Lineage tracing techniques have revolutionized the study of solid tissue SCs. It thus appears that key characteristics of the hematopoietic SC hierarchy (rarity of SCs, specific marker expression, quiescence, asymmetric division, and unidirectional differentiation) are not generalizable to other tissues. In light of these insights, we offer a revised, generalizable definition of SC function: the ability to replace lost tissue through cell division. Recent insights from lineage tracing studies have revealed that key characteristics of the classic hematopoietic SC hierarchy are not generalizable to other tissues. In light of these insights, Post and Clevers offer a revised, generalizable definition of SC function: the ability to replace lost tissue through cell division.