Terminal Myeloid Gene Expression and Differentiation Requires the Transcription Factor PU.1

Hematopoiesis is a multi-stage developmental process which yields at least eight distinct lineages including monocytes, granulocytes, lymphocytes, megakaryocytes, and erythrocytes. During myelopoiesis, pluripotent hematopoietic stem cells become committed as myeloid precursor cells which differentiate into morphologically and functionally distinct end-stage macrophages and neutrophils. Multipotent progenitors differentiate into macrophages through successive intermediates involving monoblasts, promonocytes, monocytes, and then macrophages. Granulocytic development involves the differentiation of progenitors into myeloblasts, promyelocytes, myelocytes, and then neutrophils. Hematopoiesis in the developing mouse embryo is initiated in the yolk sac on the seventh day of gestation. Primitive macrophages first appear in yolk sac blood islands on day 9, bypassing the differentiation pathway of the monocytic series, to become fetal macrophages in various tissues [13, 22].