ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages

During hematopoiesis, myeloid progenitor cells give rise to granulocytes an d macrophages. To study the role for ICSBP, a hematopoietic cell-specific t ranscription factor in myeloid cell development, the gene was introduced in to myeloid progenitor cells established from ICSBP-/- mice. ICSBP retroviru s-transduced cells differentiated into mature macrophages with phagocytic a ctivity, which coincided with the induction of specific target DNA binding activity. Similar to macrophages in vivo, ICSBP-transduced cells were growt h arrested, expressed many macrophage-specific genes, and responded to macr ophage activation signals. Contrary to this, ICSBP transduction led to repr ession of granulocyte-specific genes and inhibited G-CSF-mediated granulocy tic differentiation in these and other myeloid progenitor cells. Together, ICSBP has a key role in the myeloid cell lineage selection and macrophage m aturation.