Human Anti-DLL4 Recombinant Antibody (HPAB-0156CQ) (CAT#: HPAB-0156CQ)

Park, Mi Ae, et al. "Activation of the arterial program drives development of definitive hemogenic endothelium with lymphoid potential." Cell reports 23.8 (2018): 2467-2481. https://doi.org/10.1016/j.celrep.2018.04.092

This research investigates how activating the arterial program drives the development of definitive hemogenic endothelium with lymphoid potential from human pluripotent stem cells (hPSCs). The study demonstrates that enhancing arterial specification through ETS1 overexpression or modulation of MAPK/ERK signaling pathways at the mesodermal stage of development dramatically improves the formation of arterial-type hemogenic endothelium (AHE) with a specific phenotype (CD144+CD43-CD73-DLL4+CXCR4+/-). Blood cells generated from this arterial hemogenic endothelium showed more than 100-fold enrichment in T cell precursor frequency and possessed the capacity to produce B lymphocytes and red blood cells expressing high levels of BCL11a and β-globin, indicating definitive hematopoiesis with lymphoid potential.
Creative Biolabs provided DLL4 neutralizing antibodies that were instrumental in confirming that the effect of ETS1 upregulation on hematopoiesis is mediated through NOTCH signaling. When these antibodies were used to block DLL4, they effectively abrogated the enhancing effect of ETS1 on blood production and colony-forming cell potential, demonstrating that DLL4 expression and NOTCH activation are essential for ETS1-mediated promotion of the definitive hematoendothelial program. This contribution helped establish the molecular pathway linking arterial specification to lymphoid potential in hPSC-derived hematopoietic cells.