Plenary paper PU.1 determines the self-renewal capacity of erythroid progenitor cells

PU.1 is a hematopoietic-specific transcrip-tional activator that is absolutely required for the differentiation of B lymphocytes and myeloid-lineage cells. Although PU.1 is also expressed by early erythroid pro-genitor cells, its role in erythropoiesis, if any, is unknown. To investigate the rel-evance of PU.1 in erythropoiesis, we pro-duced a line of PU.1-deficient mice carry-ing a green fluorescent protein reporter at this locus. We report here that PU.1 is tightly regulated during differentiation—it is expressed at low levels in erythroid progenitor cells and down-regulated upon terminal differentiation. Strikingly, PU.1-deficient fetal erythroid progenitors lose their self-renewal capacity and undergo proliferation arrest, premature differentia-tion, and apoptosis. In adult mice lacking one PU.1 allele, similar defects are de-tected following stress-induced erythro-poiesis. These studies identify PU.1 as a novel and critical regulator of erythropoi-esis and highlight the versatility of this transcription factor in promoting or pre-venting differentiation depending on the hematopoietic lineage. (Blood. 2004;103