期刊
DIABETOLOGIA
卷 59, 期 7, 页码 1474-1479出版社
SPRINGER
DOI: 10.1007/s00125-016-3954-z
关键词
Beta cell; Pancreas development; Peg3; Proliferation; Pw1
资金
- European Molecular Biology Organization long-term fellowship [ALTF 826-2010]
- European Foundation for the Study of Diabetes/JDRF Young Investigator Award
- University College London Excellence Fellowship
- European Research Council [ERC-Stg-2014-639429]
- Rosetrees Trust [M362]
- Vrije Universiteit Brussel Research Council
- Stichting Diabetes Onderzoek Nederland
- Fund for Scientific Research Flanders
- Interuniversity Attraction Pole networks
- European Community Seventh Framework Programme project ENDOSTEM (Activation of vasculature associated stem cells and muscle stem cells for the repair and maintenance of muscle tissue) [241440]
- ANR 'Laboratoire d'Excellence' REVIVE programme
- Institut de Cardiometabolisme et Nutrition (IHU-ICAN) projects
- Fondation Leducq
- Rosetrees Trust [M553, M362, M362-F1] Funding Source: researchfish
Aims/hypothesis Pw1 or paternally-expressed gene 3 (Peg3) encodes a zinc finger transcription factor that is widely expressed during mouse embryonic development and later restricted to multiple somatic stem cell lineages in the adult. The aim of the present study was to define Pw1 expression in the embryonic and adult pancreas and investigate its role in the beta cell cycle in Pw1 wild-type and mutant mice. Methods We analysed PW1 expression by immunohistochemistry in pancreas of nonpregant and pregnant mice and following injury by partial duct ligation. Its role in the beta cell cycle was studied in vivo using a novel conditional knockout mouse and in vitro by lentivirus-mediated gene knockdown. Results We showed that PW1 is expressed in early pancreatic progenitors at E9.5 but becomes progressively restricted to fully differentiated beta cells as they become established after birth and withdraw from the cell cycle. Notably, PW1 expression declines when beta cells are induced to proliferate and loss of PW1 function activates the beta cell cycle. Conclusions/interpretation These results indicate that PW1 is a co-regulator of the beta cell cycle and can thus be considered a novel therapeutic target in diabetes.
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