Characterization and visualization of murine coagulation factor VIII-producing cells in vivo
Morisada Hayakawa, Asuka Sakata, Hiroko Hayakawa, Hikari Matsumoto, Takafumi Hiramoto, Yuji Kashiwakura, Nemekhbayar Baatartsogt, Noriyoshi Fukushima, Yoichi Sakata, Katsue Suzuki‐Inoue, Tsukasa Ohmori
Abstract
Abstract Coagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31 high , CD146 high , and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1) + . EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin − and C-type lectin-like receptor-2 (CLEC-2) + . In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31 high , CD146 high , Lyve1 + , CLEC-2 + , and podoplanin − in liver sinusoidal endothelial cells.