The major myeloid blood cell lineages are generated from hematopoietic stem cells
by differentiation through a series of increasingly committed progenitor cells. Precise
characterization of intermediate progenitors is important for understanding fundamental
differentiation processes and a variety of disease states, including leukemia. Here,
we evaluated the functional in vitro and in vivo potentials of a range of prospectively
isolated myeloid precursors with differential expression of CD150, Endoglin, and CD41.
Our studies revealed a hierarchy of myeloerythroid progenitors with distinct lineage
potentials. The global gene expression signatures of these subsets were consistent
with their functional capacities, and hierarchical clustering analysis suggested likely
lineage relationships. These studies provide valuable tools for understanding myeloid
lineage commitment, including isolation of an early erythroid-restricted precursor,
and add to existing models of hematopoietic differentiation by suggesting that progenitors
of the innate and adaptive immune system can separate late, following the divergence
of megakaryocytic/erythroid potential.