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

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

Research output: Contribution to journalArticle

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 β-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.

Original languageEnglish
Pages (from-to)1753-1763
Number of pages11
JournalBlood
Volume114
Issue number9
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Immunology
  • Hematology

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  • Cite this

    Starnes, L. M., Sorrentino, A., Pelosi, E., Ballarino, M., Morsilli, O., Biffoni, M., Santoro, S., Felli, N., Castelli, G., De Marchis, M. L., Mastroberardino, G., Gabbianelli, M., Fatica, A., Bozzoni, I., Nervi, C., & Peschle, C. (2009). NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls β-globin and G-CSF receptor expression. Blood, 114(9), 1753-1763. https://doi.org/10.1182/blood-2008-12-196196