Multiple Mesoderm Subsets Give Rise to Endothelial Cells, Whereas Hematopoietic Cells Are Differentiated Only from a Restricted Subset in Embryonic Stem Cell Differentiation Culture

Stem Cells ◽  
2008 ◽  
Vol 26 (2) ◽  
pp. 401-411 ◽  
Author(s):  
Takumi Era ◽  
Naoki Izumi ◽  
Misato Hayashi ◽  
Shinsuke Tada ◽  
Satomi Nishikawa ◽  
...  
2000 ◽  
Vol 28 (12) ◽  
pp. 1363-1372 ◽  
Author(s):  
Marie-Dominique Filippi ◽  
Françoise Porteu ◽  
Françoise Le Pesteur ◽  
Philippe Rameau ◽  
Maria Manuela Nogueira ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 1948-1955 ◽  
Author(s):  
Hideyo Hirai ◽  
Igor M Samokhvalov ◽  
Tetsuhiro Fujimoto ◽  
Satomi Nishikawa ◽  
Jiro Imanishi ◽  
...  

Abstract During early mouse embryogenesis, fetal liver kinase-1 (Flk-1), a receptor for vascular endothelial growth factor, and Runx1, a runt domain transcription factor, have prerequisite roles in the generation of hematopoietic lineages. Flk-1 expression is maintained in successive stages from mesodermal to endothelial cells and is down-regulated in nascent hematopoietic cells, whereas Runx1 (Runt-related transcription factor 1) is expressed in embryonic sites of hematopoietic cell de novo generation and in practically all hematopoietic organs. Here we show that Runx1 represses Flk-1 during the development of hemogenic endothelial cells into hematopoietic cells. We established embryonic stem cell clones carrying the Venus gene, a modified version of yellow fluorescence protein, in the Runx1 locus and cultured them on OP9 cells. Flk-1+ cells appeared on day 3.5, and Runx1+ cells first appeared from the Flk-1+ fraction on day 4.5. The Flk-1+Runx1+ cells rapidly stopped expressing Flk-1 with further incubation and eventually gave rise to CD45+ or TER119+ cells. Runx1 repressed Flk-1 promoter transcriptional activity in an endothelial cell line, and this repression required intact DNA-binding and transactivating domains of Runx1 protein. The repressor activity of Runx1 endogenous Flk-1 was also confirmed overexpressing Runx1 in embryonic stem cell differentiation cultures. These results provide novel insight into the role Runx1 during the development of hematopoietic cell lineages.


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