Atypical E2f functions are critical for pancreas polyploidization
Open accessAbstract
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.
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These mitotic inhibitors are expressed in several other tissues besides the liver where they are also implicated in arresting the cell cycle.
“These mitotic inhibitors are expressed in several other tissues besides the liver where they are also implicated in arresting the cell cycle (Matondo et al. 2018;Mizuno et al. 2019;Pandit et al. 2012;Qi et al. 2015).”
From Hepatocyte Cell Cycle Progression Depends on a Transcriptional Repressor Cascade Downstream of Wnt Signaling (2021) · cites this paper as Matondo et al. 2018
The Results (§3.1; page unavailable) detect E2f7/8 transcripts in multiple adult tissues, and the Discussion (§4; page unavailable) says these factors repress genes important for cell-cycle progression in pancreatic, liver, and placental cells. The paper links them to abortive cell cycles and polyploidization, but does not establish that they arrest the cell cycle in those tissues generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredE2f7 and E2f8 are expressed in several other tissues, such as placenta and pancreas, where they are implicated in arresting the cell cycle.
“These mitotic inhibitors are expressed in several other tissues, such as the placenta and pancreas, where they are also implicated in arresting the cell cycle (8, 47–49).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [48]
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- Authors
- Matondo, R. B., Moreno, E., Toussaint, M. J. M., Tooten, P. C. J., van Essen, S. C., van Liere, E. A., Youssef, S. A., Bongiovanni, L., & de Bruin, A.
- Affiliations
- Utrecht University (NL)
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-01-12
- Volume
- 13
- Issue
- 1
- Pages
- e0190899
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5766144
- OpenAlex
- W2783913712
- Cited by
- 14
- References
- 28
- Citations by year
- 2026: 1 · 2024: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- UniTERAMO Research Catalog (University of Teramo) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- NFP (R.B.M., DU.282001.1.3)
- Netherlands Organization for Scientific Research (A.d.B., NWO-ALW-IN/11-28; 834.11.002)
- Dutch Molecular Pathology Centre (NA)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- E2F7, E2F8, polyploid cells, pancreas, conditional gene deletion, postnatal survival, insulin, amylase, lipase, endocrine pancreas, exocrine pancreas
- MeSH terms
- Amylases, Animals, Blood Glucose, Growth, Insulin, Lipase, Pancreas, Polyploidy, Survival Analysis, E2F Transcription Factors, Mice
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