PU.1 FUNCTIONS IN A CELL-AUTONOMOUS MANNER TO CONTROL THE DIFFERENTIATION OF MULTIPOTENTIAL LYMPHOID-MYELOID PROGENITORS

Transcription factor PU.1 is required for the development of lymphoid and myeloid progenitors during fetal hematopoiesis. By generating chim eric animals using PU.1(-/-) ES cells or PU.1(-/-) hematopoietic proge nitors, we demonstrate that PU.1 functions in an exclusively cell-auto nomous manner to regulate the development of the lymphoid-myeloid syst em. Multipotential lymphoid-myeloid progenitors (AA4.1+, Lin(-)) are s ignificantly reduced in PU.1(-/-) embryos and fail to differentiate in to B lymphoid or myeloid cells in vitro. These results suggest that th e lymphoid and myeloid lineages develop in the fetal liver from a comm on hematopoietic progenitor not shared with erythrocytes and megakaryo cytes. Finally, the lkaros gene is expressed in PU.1 mutant embryos, s uggesting that PU.1 and lkaros are independently required for specific ation of embryonic lymphoid cell fates.