A revised map of the human progenitor hierarchy reveals origin of macrophages and dendritic cells in early lymphoid development

The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision. The validity of this model has recently been questioned in the mouse, however little is known concerning lineage potential of human progenitors. Here we provide a comprehensive analysis of the human hematopoietic hierarchy by clonally mapping the developmental potential of 7 progenitor classes from neonatal cord blood and adult bone marrow. Human multi-lymphoid progenitors, identified as a distinct population of Thy1-/loCD45RA+ cells within the CD34+CD38- stem cell compartment, gave rise to all lymphoid cell types, as well as monocytes, macrophages, and dendritic cells, indicating that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation. Total RNA was extracted from 5 - 10,000 sorted cord blood progenitor cells to compare gene expression