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 E2f transcription factors, E2f7 and 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 E2f7 or E2f8 alone 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.
Highlights
Polyploidy has been described in mammals for well over 100 years [1] and is characterized by the addition of one or more complete sets of chromosomes within a cell
Mice transgenic for the tamoxifen-inducible CreERT2 at the Rosa26 locus [15] were crossed to E2f7LoxP/LoxP E2f8LoxP/LoxP mice that harbour LoxP sites flanking sequences that are required for DNA binding [13]
Analysis of conventional E2f7-/- and E2f8-/- knockout mice revealed reduced polyploidy in the pancreas of E2f7- as well as E2f8-deficient mice (S6A–S6F Fig). Together these findings demonstrate that E2f7 and E2f8 are essential for the generation of developmentally-programmed polyploid cells in the endocrine and exocrine pancreas
Summary
Polyploidy has been described in mammals for well over 100 years [1] and is characterized by the addition of one or more complete sets of chromosomes within a cell. Polyploid cells contain either increased number of nuclei per cell or multiple genome duplications within a single nucleus [2]. This phenomenon occurs in plants, flies, worms, and fungi and is well tolerated [3]. Polyploid cells have been observed in different tissues including the placenta, bone marrow, heart, liver, and pancreas [2, 4]. In the pancreas both the endocrine and exocrine cells undergo programmed polyploidization when mice are weaned resulting in a heterogeneous population of cells with different ploidy status [4, 5]. The biological significance of polyploid cells in the pancreas is not known. The timing of the appearance of polyploid pancreatic cells coincides with the formation of polyploid hepatocytes in the liver [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
