title: Adult human circulating CD34⁻Lin⁻CD45⁻CD133⁻ cells can differentiate into hematopoietic and endothelial cells.
abstract: A precise identification of adult human hemangioblast is still lacking. To identify circulating precursors having the developmental potential of the hemangioblast, we established a new ex vivo long-term culture model supporting the differentiation of both hematopoietic and endothelial cell lineages. We identified from peripheral blood a population lacking the expression of CD34, lineage markers, CD45 and CD133 (CD34⁻Lin⁻CD45⁻CD133⁻ cells), endowed with the ability to differentiate after a 6-week culture into both hematopoietic and endothelial lineages. The bilineage potential of CD34⁻Lin⁻CD45⁻CD133⁻ cells was determined at the single-cell level in vitro and was confirmed by transplantation into NOD/SCID mice. In vivo, CD34⁻Lin⁻CD45⁻CD133⁻ cells showed the ability to reconstitute hematopoietic tissue and to generate functional endothelial cells that contribute to new vessel formation during tumor angiogenesis. Molecular characterization of CD34⁻Lin⁻D45⁻CD133⁻ cells unveiled a stem cell profile compatible with both hematopoietic and endothelial potentials, characterized by the expression of c-Kit and CXCR4 as well as EphB4, EphB2, and ephrinB2. Further molecular and functional characterization of CD34⁻Lin⁻CD45⁻CD133⁻ cells will help dissect their physiologic role in blood and blood vessel maintenance and repair in adult life.
authors.affiliation: Department of Transfusion Medicine, Laboratory of Stem Cells, Spirito Santo Hospital, Pescara, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ciraci
authors.forename: Silvia
authors.initials: S
authors.lastname: Della Bella
authors.forename: Ombretta
authors.initials: O
authors.lastname: Salvucci
authors.forename: Cristina
authors.initials: C
authors.lastname: Rofani
authors.forename: Marta
authors.initials: M
authors.lastname: Segarra
authors.forename: Caterina
authors.initials: C
authors.lastname: Bason
authors.forename: Agnese
authors.initials: A
authors.lastname: Molinari
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
authors.forename: Anna C
authors.initials: AC
authors.lastname: Berardi
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology; D019070:Cell Lineage / Q000276:immunology / Q000502:physiology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D055018:Hemangioblasts / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006410:Hematopoiesis / Q000276:immunology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000276:immunology / Q000502:physiology; D010455:Peptides / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; C516770:Ptprc protein, mouse