title: Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero.
abstract: Vasculogenesis describes the process of de novo vessel formation from vascular precursor cells. Although formation of the first major vessels, such as the dorsal aorta and cardinal veins, occurs during embryonic vasculogenesis, the contribution of precursor cell populations to postnatal vessel development is not well understood. Here, we identified a novel population of postnatal vascular precursor cells in mice. These cells express the Schwann cell protein myelin protein zero (Po) and exhibit a CD45(-)CD31(-)VEcad(-)c-kit(+)CXCR4(+) surface phenotype. Po(+) vascular precursors (PVPs) are recruited into the growing vasculature, and comprise a minor population of arterial endothelial cells in adult mice. Recruitment of PVPs into growing vessels is mediated by CXCL12-CXCR4 signaling, and is enhanced during vascular expansion induced by Notch inhibition. Po-specific ablation of Flk1, a receptor for VEGF, results in branching defects and insufficient arterial patterning in the retina, as well as reduced neovascularization of tumors and ischemic tissues. Thus, in postnatal mice, although growing vessels are formed primarily by angiogenesis from preexisting vessels, a minor population of arterial endothelia may be derived from tissue-resident vascular precursor cells.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan. ykubo33@a3.keio.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubota
authors.forename: Keiyo
authors.initials: K
authors.lastname: Takubo
authors.forename: Masanori
authors.initials: M
authors.lastname: Hirashima
authors.forename: Narihito
authors.initials: N
authors.lastname: Nagoshi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kishi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okuno
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakamura-Ishizu
authors.forename: Keigo
authors.initials: K
authors.lastname: Sano
authors.forename: Masato
authors.initials: M
authors.lastname: Murakami
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ema
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Omatsu
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018993:Myelin P0 Protein / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D018993:Myelin P0 Protein; D019718:Receptors, CXCR4; D051880:Receptors, Notch; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2