title: Expression and localization of sterile alpha motif domain containing 5 is associated with cell type and malignancy of biliary tree.
abstract: Cholangiocarcinoma (CC) is a type of relatively rare neoplasm in adenocarcinoma. The characteristics of CCs as well as biliary epithelial cells are heterogeneous at the different portion of the biliary tree. There are two candidate stem/progenitor cells of the biliary tree, i.e., biliary tree stem/progenitor cell (BTSC) at the peribiliary gland (PBG) of large bile ducts and liver stem/progenitor cell (LPC) at the canals of Hering of peripheral small bile duct. Although previous reports suggest that intrahepatic CC (ICC) can arise from such stem/progenitor cells, the characteristic difference between BTSC and LPC in pathological process needs further investigation, and the etiology of CC remains poorly understood. Here we show that Sterile alpha motif domain containing 5 (SAMD5) is exclusively expressed in PBGs of large bile ducts in normal mice. Using a mouse model of cholestatic liver disease, we demonstrated that SAMD5 expression was upregulated in the large bile duct at the hepatic hilum, the extrahepatic bile duct and PBGs, but not in proliferating intrahepatic ductules, suggesting that SAMD5 is expressed in BTSC but not LPC. Intriguingly, human ICCs and extrahepatic CCs exhibited striking nuclear localization of SAMD5 while the normal hilar large bile duct displayed slight-to-moderate expression in cytoplasm. In vitro experiments using siRNA for SAMD5 revealed that SAMD5 expression was associated with the cell cycle regulation of CC cell lines.
  
  
  CONCLUSIONS
  SAMD5 is a novel marker for PBG but not LPC in mice. In humans, the expression and location of SAMD5 could become a promising diagnostic marker for the cell type as well as malignancy of bile ducts and CCs.
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yagai
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.|Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Fuyuki F
authors.initials: FF
authors.lastname: Inagaki
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Saijou
authors.affiliation: Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.|Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.affiliation: Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.|Laboratory of Stem Cell Regulation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Minoru
authors.identifier: http://orcid.org/0000-0003-2500-7973
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001661:Biliary Tract Neoplasms / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D000071682:Sterile Alpha Motif