differential regulation of bone marrow-derived endothelial progenitor cells and endothelial outgrowth cells by the notch signaling pathway微分调节骨骨髓来源的内皮祖细胞和内皮细胞产物的信号通路.pdfVIP

Differential Regulation of Bone Marrow-Derived Endothelial Progenitor Cells and Endothelial Outgrowth Cells by the Notch Signaling Pathway 1. 2. 2. 2. 2 2 1 Jing-Yuan Chen , Lei Feng , Hai-Long Zhang , Jun-Chang Li , Xin-Wei Yang , Xiu-Li Cao , Li Liu , 2 1 1,2 Hong-Yan Qin , Ying-Min Liang *, Hua Han * 1 Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China, 2 State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, People’s Republic of China Abstract Endothelial progenitor cells (EPCs) are heterogeneous populations of cells that participate in vasculogenesis and promote tissue regeneration. However the different roles of EPC populations in vasculogenesis and tissue regeneration, as well as their regulation and mechanisms remain elusive. In the present study, we cultured bone marrow (BM)-derived early EPCs (EEPCs) and endothelial outgrowth cells (EOCs), and investigated their roles in liver regeneration and their regulation by the Notch signaling pathway. We found that Notch signaling exhibited different effects on the proliferation and migration of EEPCs and EOCs. Our results also showed that while EEPCs failed to form vessel-like structures in a three dimensional sprouting model in vitro, EOCs could sprout and form endothelial cords, and this was regulated by the Notch signaling. We further showed that, by using a conditional knockout model of RBP-J (the critical transcription factor mediating Notch signaling), Notch signaling diff