Negative regulation of hematopoiesis by the fused in myeloproliferative disorders gene product.
The t(8;13) translocation, found in a rare and aggressive type of stem cell myeloproliferative disorder, leads to the generation of a fusion protein between the N-terminal gene product of fused in myeloproliferative disorders (FIM)/ZNF198 and the fibroblast growth factor receptor 1 (FGFR1) kinase domain. The chimeric protein was reported to have constitutively activated tyrosine kinase activity. However, little is known about a role of FIM in hematopoietic cell regulation. Here we show that FIM protein is ubiquitously expressed in mouse embryonic tissues but much less in hematopoietic cells. We also show that forced expression of FIM inhibits the emergence of hematopoietic cells in the cultured mouse aorta-gonad-mesonephros (AGM) region on embryonic day (E) 11.5, where definitive hematopoiesis is first found during embryogenesis. These results suggest that the expression level of FIM determines the development of hematopoiesis during mouse ontogeny.
Inoue
Hirofumi
H
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Nobuhisa
Ikuo
I
Okita
Keisuke
K
Takizawa
Makiko
M
Pébusque
Marie Josèphe
MJ
Taga
Tetsuya
T
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D002448:Cell Adhesion; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050989:GATA2 Transcription Factor; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000166:cytology / Q000196:embryology; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D051379:Mice; D009196:Myeloproliferative Disorders / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C494712:Gata2 protein, mouse; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1