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Diabetologia. 2016 Jul;59(7):1474-1479. doi: 10.1007/s00125-016-3954-z. Epub 2016 Apr 29.

The zinc finger transcription factor PW1/PEG3 restrains murine beta cell cycling.

Author information

1
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
2
Stem Cells and Regenerative Medicine Team, Institute of Cardiology and Nutrition, Inserm UMRS-1166, University Pierre and Marie Curie (Paris VI), Paris, France.
3
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. harry.heimberg@vub.ac.be.
4
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. p.bonfanti@ucl.ac.uk.
5
Institute of Child Health, University College London, 30 Guilford Street, WC1N 1EH, London, UK. p.bonfanti@ucl.ac.uk.
6
Institute of Immunity and Transplantation, University College London, London, UK. p.bonfanti@ucl.ac.uk.

Abstract

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.

KEYWORDS:

Beta cell; Pancreas development; Peg3; Proliferation; Pw1

PMID:
27130279
PMCID:
PMC4901110
DOI:
10.1007/s00125-016-3954-z
[Indexed for MEDLINE]
Free PMC Article

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