title: Genetic marking of hematopoietic stem and endothelial cells: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain.
abstract: Using an in silico database search, we identified a novel gene encoding a cell surface molecule with a thrombospondin domain, and designated the gene as transmembrane molecule with thrombospondin module (Tmtsp). Expression profiling of Tmtsp using specific monoclonal antibodies and Venus, a variant of yellow fluorescent protein knock-in mice in the Tmtsp locus, demonstrated its specific expression in hematopoietic and endothelial cells. In lymphohematopoietic cells, Tmtsp was predominantly expressed in hematopoietic stem and progenitor cells, and the level of expression gradually declined as the cells differentiated. Venus expression faithfully traced the expression of Tmtsp, and the level of Venus expression correlated well to the in vitro hematopoietic activity as well as the in vivo bone marrow repopulating capacity. Notably, Venus expression marked the development of definitive hematopoiesis in both the extraembryonic yolk sac and the intraembryonic aorta-gonad-mesonephros (AGM) region and, in combination with CD41, strikingly promoted the enrichment of developing progenitors in the CD41(+)Venus(high) fraction at embryonic day 10.5 (E10.5). In this context, Tmtsp is a novel marker gene for primitive hematopoietic cells and endothelial cells, and Tmtsp(Venus/)(+) mice would serve as a valuable mouse model for the analysis of both embryonic and adult hematopoiesis, as well as for vascular biology.
authors.affiliation: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, University of Tokyo, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Takayanagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Hiroyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yohei
authors.initials: Y
authors.lastname: Morita
authors.forename: Joichi
authors.initials: J
authors.lastname: Usui
authors.forename: Koji
authors.initials: K
authors.lastname: Eto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Motohashi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shiomi
authors.forename: Kazuko
authors.initials: K
authors.lastname: Keino-Masu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Masu
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Shigeo
authors.initials: S
authors.lastname: Mori
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwama
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D042783:Endothelial Cells / Q000737:chemistry*; D015723:Gene Library; D005819:Genetic Markers; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D013154:Spleen; D019700:Thrombospondin 1 / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D019699:Thrombospondins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; C511241:THSD1 protein, human; D019700:Thrombospondin 1; D019699:Thrombospondins; C511242:Tmtsp protein, mouse