Commitment to the monocytic lineage occurs in the absence of the transcription factor PU.1

Mice homozygous for the disruption of the PU.1 (Spi-1) gene do not produce mature macrophages, In determining the role of PU.1 in macrophage different iation, the present study investigated whether or not there was commitment to the monocytic lineage in the absence of PU.1. Early PU.1-/myeloid coloni es were generated from neonate liver under conditions that promote primaril y macrophage and granulocyte/macrophage colonies. These PU.1-/- colonies we re found to contain cells with monocytic characteristics as determined by n onspecific esterase stain and the use of monoclonal antibodies that recogni ze early monocyte precursors, including Moma-5, ER-MP12, ER-MP20, and ER-MP 58. In addition, early myeloid cells could be grown from PU.1 -/- fetal liv er cultures in the presence of granulocyte-macrophage colony-stimulating fa ctor (GM-CSF), Similar to the PU.1 null colonies, the GM-CSF-dependent cell s also possessed early monocytic characteristics, including the ability to phagocytize latex beads. The ability of PU.1-/- progenitors to commit to th e monocytic lineage was also verified in vivo by Row cytometry and cytochem ical analysis of primary neonate liver cells. The combined data shows that PU.1 is absolutely required for macrophage development after commitment to this lineage. (C) 1999 by The American Society of Hematology.