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.

NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls β-globin and G-CSF receptor expression / Starnes, Lm; Sorrentino, A; Pelosi, E; Ballarino, Monica; Morsilli, O; Biffoni, M; Santoro, S; Felli, N; Castelli, G; DE MARCHIS, MARIA LAURA; Mastroberardino, G; Gabbianelli, M; Fatica, Alessandro; Bozzoni, Irene; Nervi, Clara; Peschle, C.. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 114:9(2009), pp. 1753-1763. [10.1182/blood-2008-12-196196]

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

BALLARINO, MONICA;DE MARCHIS, MARIA LAURA;FATICA, Alessandro;BOZZONI, Irene;NERVI, Clara;
2009

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.
2009
antigens; beta-globins; biological; biosynthesis; cd34; cell differentiation; cell lineage; cytology; erythrocytes; erythropoietin; fetal blood; gene expression regulation; genetic; granulocyte colony-stimulating factor; granulocytes; hematopoietic stem cells; humans; metabolism; models; nfi transcription factors; promoter regions; receptors
01 Pubblicazione su rivista::01a Articolo in rivista
NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls β-globin and G-CSF receptor expression / Starnes, Lm; Sorrentino, A; Pelosi, E; Ballarino, Monica; Morsilli, O; Biffoni, M; Santoro, S; Felli, N; Castelli, G; DE MARCHIS, MARIA LAURA; Mastroberardino, G; Gabbianelli, M; Fatica, Alessandro; Bozzoni, Irene; Nervi, Clara; Peschle, C.. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 114:9(2009), pp. 1753-1763. [10.1182/blood-2008-12-196196]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/230626
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