title: Differential regulation of bone marrow-derived endothelial progenitor cells and endothelial outgrowth cells by the Notch signaling pathway.
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 differentially regulates EEPCs and EOCs. In a partial hepatectomy (PHx) model, EEPCs Notch-dependently benefitted liver regeneration with respect to liver function and hepatocyte proliferation and apoptosis. In contrast, EOCs appeared not directly involved in the recovery of liver function and the increase of hepatocytes. These data suggested that the RBP-J-mediated Notch signaling differentially regulated the two types of EPCs, which showed different roles in liver regeneration.
authors.affiliation: Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Zhang
authors.forename: Jun-Chang
authors.initials: JC
authors.lastname: Li
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Yang
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Ying-Min
authors.initials: YM
authors.lastname: Liang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism; D008115:Liver Regeneration; D051379:Mice; D018345:Mice, Knockout; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch