Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage.

Journal Article (Journal Article)

Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis. Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis. We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors. We further identify in this cell population the type III transforming growth factor-beta receptor gene, TGFBR3, as a direct target of Gfi-1B. Knockdown of Gfi-1B results in altered transforming growth factor-beta (TGF-beta) signaling as shown by the increase in Smad2 phosphorylation and its inability to associate to the transcription intermediary factor 1-gamma (TIF1-gamma). Because the Smad2/TIF1-gamma complex is known to specifically regulate erythroid differentiation, we propose that, by repressing TGF-beta type III receptor (TbetaRIotaII) expression, Gfi-1B favors the Smad2/TIF1-gamma interaction downstream of TGF-beta signaling, allowing immature progenitors to differentiate toward the erythroid lineage.

Full Text

Duke Authors

Cited Authors

  • Randrianarison-Huetz, V; Laurent, B; Bardet, V; Blobe, GC; Huetz, F; Duménil, D

Published Date

  • April 8, 2010

Published In

Volume / Issue

  • 115 / 14

Start / End Page

  • 2784 - 2795

PubMed ID

  • 20124515

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-09-241752


  • eng

Conference Location

  • United States