PU.1 BUT NOT ETS-2 IS ESSENTIAL FOR MACROPHAGE DEVELOPMENT FROM EMBRYONIC STEM-CELLS

Transcription factors play an important role choreographing lineage co mmitment and expansion of blood cells. Nuclear factors that are expres sed primarily or exclusively in hematopoietic cells are likely candida tes for regulating blood cell development. The transcription factor PU .1 is found only in hematopoietic cells, whereas ets-2, a related fami ly member, is ubiquitously expressed. To compare the role of these two transcription factors in macrophage development, embryonic stem (ES) cells with a homozygous disruption of either the PU.1 or the ets-2 gen e were generated. The ability of both knockout ES cells to differentia te to macrophages was tested. Normal development of macrophages, as de termined by histochemical and immunohistochemical analysis, from PU.1 knockout ES cells was significantly blocked. Furthermore, the expressi on of known markers associated with macrophages, such as c-fms, CD11b, CD18 and granulocyte-macrophage colony-stimulating factor receptor, w ere not detected by reverse transcriptase-polymerase chain reaction. I n contrast to the PU.1 knockout ES cells, macrophage development from the ets-2 knockout ES cells was normal. Although both PU.1 and ets-2 a re found in macrophages, these data show a distinct role for the linea ge-restricted PU.1 transcription factor in macrophage development. (C) 1996 by The American Society of Hematology.