@misc{10481/111607,
year = {2015},
month = {8},
url = {https://hdl.handle.net/10481/111607},
abstract = {Notch signaling is essential for definitive hematopoiesis, but its role in human embryonic hematopoiesis is largely unknown. We show that in hESCs the expression of the Notch ligand DLL4 is induced during hematopoietic differentiation. We found that DLL4 is only expressed in a sub-population of bipotent hematoendothelial progenitors (HEPs) and segregates their hematopoietic versus endothelial potential. We demonstrate at the clonal level and through transcriptome analyses that DLL4(high) HEPs are enriched in endothelial potential, whereas DLL4(low/-) HEPs are committed to the hematopoietic lineage, albeit both populations still contain bipotent cells. Moreover, DLL4 stimulation enhances hematopoietic differentiation of HEPs and increases the amount of clonogenic hematopoietic progenitors. Confocal microscopy analysis of whole differentiating embryoid bodies revealed that DLL4(high) HEPs are located close to DLL4(low/-) HEPs, and at the base of clusters of CD45+ cells, resembling intra-aortic hematopoietic clusters found in mouse embryos. We propose a model for human embryonic hematopoiesis in which DLL4(low/-) cells within hemogenic endothelium receive Notch-activating signals from DLL4(high) cells, resulting in an endothelial-to-hematopoietic transition and their differentiation into CD45+ hematopoietic cells.},
publisher = {Springer Nature},
title = {The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and regulates their hematopoietic fate},
doi = {10.1038/leu.2015.74},
author = {Ayllon, Veronica and Bueno, Clara and Ramos Mejía, Verónica and Navarro-Montero, Oscar and Prieto, Cristina and Real Luna, Pedro José and Romero, Tamara and García-León, María José and Toribio, Maria Luisa and Bigas, Anna and Menendez, Pablo},
}