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

Randrianarison-Huetz, Voahangy, Laurent, Benoit, Bardet, Valérie, Blobe, Gerard C., Huetz, François, Duménil, Dominique·2010·Blood
DOI 10.1182/blood-2009-09-241752
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Abstract

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-β receptor gene, TGFBR3, as a direct target of Gfi-1B. Knockdown of Gfi-1B results in altered transforming growth factor-β (TGF-β) signaling as shown by the increase in Smad2 phosphorylation and its inability to associate to the transcription intermediary factor 1-γ (TIF1-γ). Because the Smad2/TIF1-γ complex is known to specifically regulate erythroid differentiation, we propose that, by repressing TGF-β type III receptor (TβRΙII) expression, Gfi-1B favors the Smad2/TIF1-γ interaction downstream of TGF-β signaling, allowing immature progenitors to differentiate toward the erythroid lineage.

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Metadata

Authors
Randrianarison-Huetz, V., Laurent, B., Bardet, V., Blobe, G. C., Huetz, F., & Duménil, D.
Affiliations
  • Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France;
  • Departments of Medicine and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC; and
  • Unité d'Immunité Cellulaire Antivirale, Institut Pasteur, Paris, France
Venue
Blood
Publisher
American Society of Hematology
Published
2010-04-08
Volume
115
Issue
14
Pages
2784-2795
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2009-09-241752
Cited by
82
References
2
Language
en

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CoChat. (2026). Citation check: Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-β signaling at the bipotent erythro-megakaryocytic progenitor stage. https://app.cochat.ai/papers/10.1182/blood-2009-09-241752
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Randrianarison-Huetz, V., Laurent, B., Bardet, V., Blobe, G. C., Huetz, F., & Duménil, D. (2010). Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-β signaling at the bipotent erythro-megakaryocytic progenitor stage. Blood. https://doi.org/10.1182/blood-2009-09-241752