The T cell leukemia oncoprotein SCL/tal-1, a basic–helix-loop-helix transcription factor, is required for production of embryonic red blood cells in the mouse yolk sac. To define roles in other lineages, we studied the hematopoietic potential of homozygous mutant SCL/tal-1 −/− embryonic stem cells upon in vitro differentiation and in vivo in chimeric mice. Here we show that in the absence of SCL/tal-1, hematopoiesis, including the generation of red cells, myeloid cells, megakaryocytes, mast cells, and both T and B lymphoid cells, is undetectable. These findings suggest that SCL/tal-1 functions very early in hematopoietic development, either in specification of ventral mesoderm to a blood cell fate, or in formation or maintenance of immature progenitors.
