PU.1 IS NOT ESSENTIAL FOR EARLY MYELOID GENE-EXPRESSION BUT IS REQUIRED FOR TERMINAL MYELOID DIFFERENTIATION

We have previously shown using gene targeting that PU.1 is essential f or the development of lymphoid and myeloid lineages during fetal liver hematopoiesis. We now show that PU.1 is required for the maturation o f yolk sac-derived myeloid progenitors and for the differentiation of ES cells into macrophages. The role of PU.1 in regulating target genes , thought to be critical in the development of monocytes and granulocy tes, has been analyzed. Early genes such as GM-CSFR, G-CSFR, and myelo peroxidase are expressed in PU.1(-/-) embryos and differentiated PU.1( -/-) ES cells. However, the expression of genes associated with termin al myeloid differentiation (CD11b, CD64, and M-CSFR) is eliminated in differentiated PU.1(-/-) ES cells. Development of macrophages is resto red with the introduction of a PU.1 cDNA regulated by its own promoter . The PU.1(-/-) ES cells represent an important model for analyzing my eloid cell development.