Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human primary hematopoietic CD34+ cells to investigate Growth Factor Independence-1B (Gfi-1B) functions


ABSTRACT: Growth Factor Independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis. Targeted gene disruption of Gfi-1B in mice leads to embryonic lethality due to 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 (MEP). We further identify in this cell population the type III transforming growth factor-? receptor gene, TGFBR3, as a direct target of Gfi-1B. Knock down of Gfi-1B results in altered TGF? signaling as shown by the increase in Smad2 phosphorylation and its inability to associate to the Transcription Intermediary Factor 1? (TIF1?). Because Smad2/TIF1? complex is known to specifically regulate erythroid differentiation, we propose that, by repressing the transforming growth factor-? receptor III (T?R?II) expression, Gfi-1B favors the Smad2/TIF1? interaction downstream of TGF? signaling, allowing immature progenitors to differentiate toward the erythroid lineage.

ORGANISM(S): Homo sapiens

SUBMITTER: Nicolas Cagnard 

PROVIDER: E-MEXP-2560 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Randrianarison-Huetz Voahangy V   Laurent Benoit B   Bardet Valérie V   Blobe Gerard C GC   Huetz François F   Duménil Dominique D  

Blood 20100202 14


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 pr  ...[more]

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