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The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells
Authors:Hideaki Naoe  Tatsuyuki Chiyoda  Jo Ishizawa  Kenta Masuda  Hideyuki Saya  Shinji Kuninaka
Affiliation:1. Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan;2. Department of Gastroenterology and Hepatology, Kumamoto University, School of Medicine, Kumamoto 860-8556, Japan;3. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan;1. Department of Biochemistry, Faculty of Medicine, Kinki University, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan;2. Acute Medicine, Faculty of Medicine, Kinki University, 377-2, Ohno-Higashi,Osaka-Sayama, Osaka 589-8511, Japan;3. Basic Medical Sciences, Faculty of Medicine, Kinki University, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan;1. Department of Food and Environmental Sciences, Division of Nutrition, P.O. Box 66 (Agnes Sjöbergin katu 2), FIN-00014 University of Helsinki, Finland;2. School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland;3. Department of Food and Environmental Sciences, Division of Food Chemistry, P.O. Box 27 (Latokartanonkaari 11), FIN-00014 University of Helsinki, Finland;1. Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya 464-8651, Japan;2. Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan;3. Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan
Abstract:Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1GT/GT) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1GT/GT TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation.
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