Basic–liver, Pancreas, and Biliary TractWnt/β-Catenin Signaling in Murine Hepatic Transit Amplifying Progenitor Cells
Section snippets
Reagents
The following antibodies were used where indicated. Monoclonal mouse antibodies against β-catenin, including dephosphorylated (Thr41/Ser45) (Upstate, Charlottesville, VA) or phosphorylated β-catenin (Thr41/Ser33/37) (Cell Signaling, Danvers, MA), anti-pan β-catenin was from BD Biosciences (San Jose, CA). Polyclonal antibodies against proliferating cell nuclear antigen (PCNA) and phosphorylated-tyrosine (PY20) were from Santa Cruz Biotechnology (Santa Cruz, CA). An antibody against β-actin from
Characterization of the DDC Model of Oval Cell Activation
To confer chronic hepatic injury and to drive oval cell proliferation, we used the DDC hepatotoxin mouse injury model.10, 35 In mice that were fed a DDC-enriched diet, small oval-shaped cells were observed to proliferate and migrate from the PT region of the hepatic parenchyma (Figure 1A). These cells infiltrated the hepatic parenchyma as sheets of cells and assumed ductlike shapes that were most prominent in proximity to the PT (Figure 1A). The cells appeared to form abnormal appearing
Discussion
Postnatal progenitor cells have been extensively studied in the skin, gut, and hematopoietic systems.46 Many of these rapidly renewing systems have similar biologic mechanisms, including a role for Wnt/β-catenin signaling in regulating stem and progenitor cell proliferation.14, 16, 47 In this study we have identified a similar biologic process governing liver regeneration during activation of the facultative transit amplifying population of oval cells in response to a chronic regenerative
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Supported by grants from the American College of Surgeons, American Pediatric Surgical Association, Oak Foundation, Packard Foundation, Office of Technology Licensing-Stanford University, and the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (pilot grant DK56339: Digestive Disease Center at Stanford) (to K.G.S.); the Swiss National Science Foundation (to C.F.); the HHMI and the National Institutes of Health (grant 1R01 DK67834-01 to R.N.).
All authors declare that they have no conflict of interest to disclose.
- 1
M.K.’s current affiliation is Department of Surgery, Jikei University, Tokyo, Japan. Y.J.J.’s current affiliation is Department of Surgery, School of Medicine, Chonbuk National University, Jeonju, Korea.
- 2
M.H. and M.K. contributed equally to this work.