PU.1 determines the self-renewal capacity of erythroid progenitor cells.
Fiche publication
Date publication
mai 2004
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN Susan, Dr KASTNER Philippe
Tous les auteurs :
Back J, Dierich A, Bronn C, Kastner P, Chan S
Lien Pubmed
Résumé
PU.1 is a hematopoietic-specific transcriptional activator that is absolutely required for the differentiation of B lymphocytes and myeloid-lineage cells. Although PU.1 is also expressed by early erythroid progenitor cells, its role in erythropoiesis, if any, is unknown. To investigate the relevance of PU.1 in erythropoiesis, we produced a line of PU.1-deficient mice carrying 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 differentiation, and apoptosis. In adult mice lacking one PU.1 allele, similar defects are detected following stress-induced erythropoiesis. These studies identify PU.1 as a novel and critical regulator of erythropoiesis and highlight the versatility of this transcription factor in promoting or preventing differentiation depending on the hematopoietic lineage.
Référence
Blood. 2004 May 15;103(10):3615-23