The role of angiopoietins in the development of endothelial cells from cord blood CD34+ progenitors.
Circulating endothelial progenitors contribute to neovascularization at sites of injury and tumorigenesis in postnatal life. Yet, the molecular mechanisms initiating the endothelial developmental program of these precursors remain elusive. Here we provide evidence that endothelial development from progenitors circulating in human cord blood requires angiopoietins, a set of growth factors also involved in vascular branching during embryogenesis. We show that cord blood cells with the potential for endothelial development reside in a CD34(+)CD11b+ subset capable of autonomously producing and binding angiopoietins. Functionally, endogenous angiopoietin-1 regulates initial endothelial cell commitment, whereas angiopoietin-2 enhances expansion of the endothelial cell progeny. These findings suggest a role for angiopoietins as regulators of endothelial development from circulating progenitors and imply a function of angiopoietins at distinct developmental steps in postnatal angiogenesis.
Hildbrand
Patrick
P
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cirulli
Vincenzo
V
Prinsen
Robyn C
RC
Smith
Kent A
KA
Torbett
Bruce E
BE
Salomon
Daniel R
DR
Crisa
Laura
L
D042683:Angiopoietin-1 / Q000096:biosynthesis*; D042702:Angiopoietin-2 / Q000096:biosynthesis*; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D039481:CD11b Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D015854:Up-Regulation
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018952:Antigens, CD34; D039481:CD11b Antigen; D018076:DNA, Complementary; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen