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February 20, 2019

Making cells to study congenital bile duct diseases

The Osafune lab reports a new protocol to make cholangiocyte progenitors from human iPS cells.

The bile ducts are responsible for transporting bile from the liver to the appropriate organs for food digestion. The ducts are lined by cholangiocytes. In normal development, the cells first emerge as a sheet known as the ductal plate, which undergo remodeling to form different structures. Failure to remodel is associated with several congenital disorders such as autosomal recessive polycystic kidney disease, a rare disorder that leaves babies with morbid or mortal kidney failure. To study the development of these cells and related diseases, the laboratory of Professor Kenji Osafune reports a new differentiation protocol to prepare cholangiocyte progenitors from human iPS cells.

The protocol depends on cells expressing the gene AQP1, which codes for aquaporin 1, a protein found in many types of cells and responsible for water transport. The researchers found that the expression of AQP1 during the differentiation protocol marked a transition from cells that resembled ductal plate cells to those resembling ductal plate cells undergoing remodeling.

Key to the AQP1 expression was the incorporation of two biological signaling factors, TGFβ2 and EGF, to the differentiation protocol. TGFβ signaling is known to stimulate the differentiation of hepatoblasts into bile duct cells, while EGF signaling contributes to the development of biliary epithelial cells. Accordingly, the differentiation protocol used known means to prepare hepatoblasts from the iPS cells. The AQP1-expressing cells remodeled into duct-like structures with transport ability.

Further investigation confirmed that the cells behave like cholangiocyte progenitors found in the fetus, suggesting their usefulness for studying related congenital disorders.

Paper Details
  • Journal: Stem Cell Research
  • Title: Differentiation and isolation of iPSC-derived remodeling ductal plate-like cells by use of an AQP1-GFP reporter human iPSC line
  • Authors: Satoshi Matsui, Miyuki Ochiai, Katsutaro Yasuda, Shin-ichi Mae, Maki Kotaka, Taro Toyoda, Takuya Yamamoto, and Kenji Osafune
  • Author Affiliations:
    • ・Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
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