PU.1 but not ets-2 is essential for macrophage development from embryonic stem cells

Transcription factors play an important role choreographing lineage commitment and expansion of blood cells. Nuclear factors that are expressed primarily or exclusively in hematopoietic cells are likely candidates for regulating blood cell development. The transcription factor PU.1 is found only in hematopoietic cells, whereas ets-2, a related family 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 gene were generated. The ability of both knockout ES cells to differentiate to macrophages was tested. Normal development of macrophages, as determined by histochemical and immunohistochemical analysis, from PU.1 knockout ES cells was significantly blocked. Furthermore, the expression of known markers associated with macrophages, such as c-fms, CD11b, CD18 and granulocyte-macrophage colony-stimulating factor receptor, were not detected by reverse transcriptase-polymerase chain reaction. In contrast to the PU.1 knockout ES cells, macrophages, development from the ets-2 knockout ES cells was normal. Although both PU.1 and ets-2 are found in macrophages, these data show a distinct role for the lineage-restricted PU.1 transcription factor in macrophage development.