Fetal liver myelopoiesis occurs through distinct, prospectively isolatable progenitor subsets

Abstract

Hematopoietic fate maps in the developing mouse embryo remain imprecise. Definitive, adult-type hematopoiesis first appears in the fetal liver, then progresses to the spleen and bone marrow. Clonogenic common lymphoid progenitors and clonogenic common myeloid progenitors (CMPs) in adult mouse bone marrow that give rise to all lymphoid and myeloid lineages, respectively, have recently been identified. Here it is shown that myelopoiesis in the fetal liver similarly proceeds through a CMP equivalent. Fetal liver CMPs give rise to megakaryocyte-erythrocyte-restricted progenitors (MEPs) and granulocyte-monocyte-restricted progenitors (GMPs) that can also be prospectively isolated by cell surface phenotype. MEPs and GMPs generate mutually exclusive cell types in clonogenic colony assays and in transplantation experiments, 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 populations. These results suggest that adult hematopoietic hierarchies are determined early in the development of the definitive immune system and suggest that the molecular mechanisms underlying cell fate decisions within the myeloerythroid lineages are conserved from embryo to adult. (Blood. 2001;98:627-635)