title: NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls beta-globin and G-CSF receptor expression.
abstract: 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.
authors: Department of Histology and Medical Embryology, University La Sapienza, Rome, Italy.
authors: Linda Marie
authors: LM
authors: Starnes
authors: Antonio
authors: A
authors: Sorrentino
authors: Elvira
authors: E
authors: Pelosi
authors: Monica
authors: M
authors: Ballarino
authors: Ornella
authors: O
authors: Morsilli
authors: Mauro
authors: M
authors: Biffoni
authors: Simona
authors: S
authors: Santoro
authors: Nadia
authors: N
authors: Felli
authors: Germana
authors: G
authors: Castelli
authors: Maria Laura
authors: ML
authors: De Marchis
authors: Gianfranco
authors: G
authors: Mastroberardino
authors: Marco
authors: M
authors: Gabbianelli
authors: Alessandro
authors: A
authors: Fatica
authors: Irene
authors: I
authors: Bozzoni
authors: Clara
authors: C
authors: Nervi
authors: Cesare
authors: C
authors: Peschle
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis; D002454:Cell Differentiation; D019070:Cell Lineage; D004912:Erythrocytes / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism; D005312:Fetal Blood / Q000378:metabolism; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008954:Models, Biological; D051839:NFI Transcription Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D055544:beta-Globins / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D051839:NFI Transcription Factors; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D055544:beta-Globins; D004921:Erythropoietin