title: Prominin-1/CD133 expression as potential tissue-resident vascular endothelial progenitor cells in the pulmonary circulation.
abstract: Pulmonary vascular endothelial cells could contribute to maintain homeostasis in adult lung vasculature. "Tissue-resident" endothelial progenitor cells (EPCs) play pivotal roles in postnatal vasculogenesis, vascular repair, and tissue regeneration; however, their local pulmonary counterparts remain to be defined. To determine whether prominin-1/CD133 expression can be a marker of tissue-resident vascular EPCs in the pulmonary circulation, we examined the origin and characteristics of prominin-1/CD133-positive (Prom1(+)) PVECs considering cell cycle status, viability, histological distribution, and association with pulmonary vascular remodeling. Prom1(+) PVECs exhibited high steady-state transit through the cell cycle compared with Prom1(-) PVECs and exhibited homeostatic cell division as assessed using the label dilution method and mice expressing green fluorescent protein. In addition, Prom1(+) PVECs showed more marked expression of putative EPC markers and drug resistance genes as well as highly increased activation of aldehyde dehydrogenase compared with Prom1(-) PVECs. Bone marrow reconstitution demonstrated that tissue-resident cells were the source of >98% of Prom1(+) PVECs. Immunofluorescence analyses revealed that Prom1(+) PVECs preferentially resided in the arterial vasculature, including the resistant vessels of the lung. The number of Prom1(+) PVECs was higher in developing postnatal lungs. Sorted Prom1(+) PVECs gave rise to colonies and formed fine vascular networks compared with Prom1(-) PVECs. Moreover, Prom1(+) PVECs increased in the monocrotaline and the Su-5416 + hypoxia experimental models of pulmonary vascular remodeling. Our findings indicated that Prom1(+) PVECs exhibited the phenotype of tissue-resident EPCs. The unique biological characteristics of Prom1(+) PVECs predominantly contribute to neovasculogenesis and maintenance of homeostasis in pulmonary vascular tissues.
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and ayumisekine@chiba-u.jp.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Nishiwaki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Nishimura
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Urushibara
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Rika
authors.initials: R
authors.lastname: Suda
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Shin
authors.initials: S
authors.lastname: Takayanagi
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Jiro
authors.initials: J
authors.lastname: Terada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Sakao
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwama
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D006706:Homeostasis; D008168:Lung / Q000098:blood supply / Q000254:growth & development; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D061251:Primary Cell Culture; D011651:Pulmonary Artery / Q000166:cytology; D014945:Wound Healing
chemical_list: D000071916:AC133 Antigen; D015415:Biomarkers; C000606024:Prom1 protein, mouse
keywords: neovasculogenesis; pulmonary vascular endothelial cells; pulmonary vascular remodeling