Fetal liver myelopoiesis occurs through distinct, prospectively isolatableprogenitor subsets

Hematopoietic fate maps in the developing mouse embryo remain imprecise. De finitive, adult-type hematopoiesis first appears in the fetal liver, then p rogresses to the spleen and bone marrow. Clonogenic common lymphoid progeni tors and clonogenic common myeloid progenitors (CMPs) in adult mouse bone m arrow that give rise to all lymphoid and myeloid lineages, respectively, ha ve recently been identified. Here it is shown that myelopoiesis in the feta l liver similarly proceeds through a CMP equivalent. Fetal liver CMPs give rise to megakaryocyte erythrocyte-restricted progenitors (MEPs) and granulo cyte-monocyte-restricted progenitors (GMPs) that can also be prospectively isolated by cell surface phenotype. MEPs and GMPs generate mutually exclusi ve cell types in clonogenic colony assays and in transplantation experiment s, suggesting that the lineage restriction observed within each progenitor subset is absolute under normal conditions. Purified progenitor populations were used to analyze expression profiles of various hematopoiesis-related genes. Expression patterns closely matched those of the adult counterpart p opulations. These results suggest that adult hematopoietic hierarchies are determined early in the development of the definitive immune system and sug gest that the molecular mechanisms underlying cell fate decisions within th e myeloerythroid lineages are conserved from embryo to adult.