Atypical E2f functions are critical for pancreas polyploidization

Ramadhan B. Matondo, Eva Moreno, Mathilda J. M. Toussaint, Peter C. J. Tooten, Saskia C. van Essen, Elsbeth A. van Liere, Sameh A. Youssef, Laura Bongiovanni, Alain de Bruin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2ftranscription factors, E2f7and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7or E2f8alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

Original languageEnglish
Article number0190899
Number of pages15
JournalPLoS ONE
Volume13
Issue number1
DOIs
Publication statusPublished - 12-Jan-2018
Externally publishedYes

Keywords

  • MAMMALIAN-CELLS
  • MUTANT MICE
  • LIVER
  • ANGIOGENESIS
  • EXPRESSION
  • STRESS
  • MOUSE

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