NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls beta-globin and G-CSF receptor expression

作者：Starnes Linda Marie; Sorrentino Antonio; Pelosi Elvira; Ballarino Monica; Morsilli Ornella; Biffoni Mauro; Santoro Simona; Felli Nadia; Castelli Germana; De Marchis Maria Laura; Mastroberardino Gianfranco; Gabbianelli Marco; Fatica Alessandro; Bozzoni Irene; Nervi Clara; Peschle Cesare^*

来源：Blood, 2009, 114(9): 1753-1763.

DOI：10.1182/blood-2008-12-196196

It is generally conceded that selective combinations of transcription factors determine hematopoietic lineage commitment and differentiation. Here we show that in normal human hematopoiesis the transcription factor nuclear factor I-A (NFI-A) exhibits a marked lineage-specific expression pattern: it is upmodulated in the erythroid (E) lineage while fully suppressed in the granulopoietic (G) series. In unilineage E culture of hematopoietic progenitor cells (HPCs), NFI-A overexpression or knockdown accelerates or blocks erythropoiesis, respectively: notably, NFI-A overexpression restores E differentiation in the presence of low or minimal erythropoietin stimulus. Conversely, NFI-A ectopic expression in unilineage G culture induces a sharp inhibition of granulopoiesis. Finally, in bilineage E + G culture, NFI-A overexpression or suppression drives HPCs into the E or G differentiation pathways, respectively. These NFI-A actions are mediated, at least in part, by a dual and opposite transcriptional action: direct binding and activation or repression of the promoters of the beta-globin and G-CSF receptor gene, respectively. Altogether, these results indicate that, in early hematopoiesis, the NFI-A expression level acts as a novel factor channeling HPCs into either the E or G lineage. (Blood. 2009;114:1753-1763)

• 出版日期2009-8-27