The f/&2 receptor tyrosine kinase has been implicated in hematopoietic development. Mice deficient in f/k2 were generated. Mutants developed into heaithy adults with normal mature hematopoietic populations. However, they possessed specific deficiencies in primitive B iymphoid progenitors. Bone marrow transplantation experiments revealed a further deficiency in T ceil and myeioid reconstitution by mutant stem ceils. Micedeficient for both c-klf and f/k2 exhibited a more severe phenotype characterized by large overall decreases in hematopoietic ceil numbers, further reductions in the relative frequencies of iymphoid progenitors, and a postnatal lethality. Taken together, the data suggest that f/k2 plays a role both in multipotent stem ceils and in iymphoid differentiation. introduction

Hematopoiesis is a self-renewing process capable of continuously producing at least eight distinct blood cell lineages (reviewed by Dexter and Spooncer, 1987; Lemischka, 1992). At the heart of this system is a population of hematopoietic stem cells, which are multipotent in their ability to differentiate and which can self-renew. Transplantation experiments have demonstrated that single stem cells are both necessary and sufficient for lifelong blood cell production (Jordan and Lemischka, 1990b; Smith et al., 1991). Traditionally, hematopoietic stem cells have been studied indirectly; that is, as activities either in transplantation contexts or in complex in vitro culture systems. Efforts in a number of laboratories have yielded procedures for substantial purification of these ceils, thus providing a means for direct mechanistic analyses of stem cell behavior (Visser et al., 1984; Spangrude et al., 1988; Ploemacher and Brons, 1989; Jordan et al., 1990). Numerous studies have implicated a panel of cytokines that act in vitro on purified stem cell populations (reviewed by Nicola, 1989; Ogawa, 1993). However, relatively little information is available regarding the mechanisms that regulate the proliferation and differentiation of stem cells in a normal in vivo context.