Repository logo

Endoglin potentiates nitric oxide synthesis to enhance definitive hematopoiesis.



Change log


Nasrallah, Rabab 
Knezevic, Kathy 
Thai, Thuan 
Thomas, Shane R 
Göttgens, Berthold 


During embryonic development, hematopoietic cells develop by a process of endothelial-to hematopoietic transition of a specialized population of endothelial cells. These hemogenic endothelium (HE) cells in turn develop from a primitive population of FLK1(+) mesodermal cells. Endoglin (ENG) is an accessory TGF-β receptor that is enriched on the surface of endothelial and hematopoietic stem cells and is also required for the normal development of hemogenic precursors. However, the functional role of ENG during the transition of FLK1(+) mesoderm to hematopoietic cells is ill defined. To address this we used a murine embryonic stem cell model that has been shown to mirror the temporal emergence of these cells in the embryo. We noted that FLK1(+) mesodermal cells expressing ENG generated fewer blast colony-forming cells but had increased hemogenic potential when compared with ENG non-expressing cells. TIE2(+)/CD117(+) HE cells expressing ENG also showed increased hemogenic potential compared with non-expressing cells. To evaluate whether high ENG expression accelerates hematopoiesis, we generated an inducible ENG expressing ES cell line and forced expression in FLK1(+) mesodermal or TIE2(+)/CD117(+) HE cells. High ENG expression at both stages accelerated the emergence of CD45(+) definitive hematopoietic cells. High ENG expression was associated with increased pSMAD2/eNOS expression and NO synthesis in hemogenic precursors. Inhibition of eNOS blunted the ENG induced increase in definitive hematopoiesis. Taken together, these data show that ENG potentiates the emergence of definitive hematopoietic cells by modulating TGF-β/pSMAD2 signalling and increasing eNOS/NO synthesis.



Endoglin, FLK1, Hematopoiesis, Hemogenic endothelium, Nitric oxide, SMAD2

Journal Title

Biol Open

Conference Name

Journal ISSN


Volume Title



The Company of Biologists
Leukaemia & Lymphoma Research (12029)
Wellcome Trust (097922/Z/11/Z)
Medical Research Council (MC_PC_12009)
Leukemia & Lymphoma Society (7001-12)
Cancer Research Uk (None)
Biotechnology and Biological Sciences Research Council (BB/I00050X/1)
Wellcome Trust (097922/Z/11/B)
The authors thank Dr Zúñiga-Pflücker (University of Toronto) for the ENG-/- and +/- murine ES cells. This work was supported by grants from the National Health and Medical Research Council of Australia, Australian Research Council and the Dr Tom Bee Stem Cell Research Fund to JEP, Cancer Research UK to VK and GL and the BBSRC, Leukaemia and Lymphoma Research, The Leukaemia and Lymphoma Society, Cancer Research UK, and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute to BG.