Display options
Share it on

Front Physiol. 2017 Oct 31;8:862. doi: 10.3389/fphys.2017.00862. eCollection 2017.

Hepatocyte Ploidy Is a Diversity Factor for Liver Homeostasis.

Frontiers in physiology

Clemens Kreutz, Sabine MacNelly, Marie Follo, Astrid Wäldin, Petra Binninger-Lacour, Jens Timmer, María M Bartolomé-Rodríguez

Affiliations

  1. Faculty of Mathematics and Physics, Institute of Physics, University of Freiburg, Freiburg, Germany.
  2. Center for Systems Biology (ZBSA), University of Freiburg, Freiburg, Germany.
  3. Freiburg Center for Data Analysis and Modelling, University of Freiburg, Freiburg, Germany.
  4. Clinic for Internal Medicine II/Molecular Biology, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
  5. Clinic for Internal Medicine I/Lighthouse Core Facility, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
  6. BIOSS, Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.

PMID: 29163206 PMCID: PMC5671579 DOI: 10.3389/fphys.2017.00862

Abstract

Polyploidy, the existence of cells containing more than one pair of chromosomes, is a well-known feature of mammalian hepatocytes. Polyploid hepatocytes are found either as cells with a single polyploid nucleus or as multinucleated cells with diploid or even polyploid nuclei. In this study, we evaluate the degree of polyploidy in the murine liver by accounting both DNA content and number of nuclei per cell. We demonstrate that mouse hepatocytes with diploid nuclei have distinct metabolic characteristics compared to cells with polyploid nuclei. In addition to strong differential gene expression, comprising metabolic as well as signaling compounds, we found a strongly decreased insulin binding of nuclear polyploid cells. Our observations were associated with nuclear ploidy but not with total ploidy within a cell. We therefore suggest ploidy of the nuclei as an new diversity factor of hepatocytes and hypothesize that hepatocytes with polyploid nuclei may have distinct biological functions than mono-nuclear ones. This diversity is independent from the well-known heterogeneity related to the cells' position along the porto-central liver-axis.

Keywords: hepatocytes; insulin; liver; metabolism; polyploidy; signaling

References

  1. Nat Rev Genet. 2005 Nov;6(11):836-46 - PubMed
  2. Proc Natl Acad Sci U S A. 1975 Mar;72(3):794-8 - PubMed
  3. Nat Rev Mol Cell Biol. 2006 Feb;7(2):85-96 - PubMed
  4. Bioinformatics. 2012 Jul 1;28(13):1698-704 - PubMed
  5. Cell Tissue Res. 1984;238(3):643-7 - PubMed
  6. J Cell Sci. 1978 Dec;34:247-78 - PubMed
  7. Genome. 2001 Jun;44(3):350-60 - PubMed
  8. Exp Cell Res. 1967 Jun;46(3):533-40 - PubMed
  9. Science. 2002 Aug 9;297(5583):1003-7 - PubMed
  10. Science. 1994 Apr 15;264(5157):421-4 - PubMed
  11. Histochem Cell Biol. 1995 Feb;103(2):81-91 - PubMed
  12. J Theor Biol. 1994 May 21;168(2):191-9 - PubMed
  13. Biochem Biophys Res Commun. 2006 Apr 21;342(4):1160-7 - PubMed
  14. Funct Integr Genomics. 2010 Nov;10(4):433-46 - PubMed
  15. Elife. 2015 Dec 27;4: - PubMed
  16. Adv Nutr. 2012 May 01;3(3):286-94 - PubMed
  17. Curr Biol. 2012 Jul 10;22(13):1166-75 - PubMed
  18. Diabetes Metab. 2004 Nov;30(5):398-408 - PubMed
  19. Comp Biochem Physiol A Mol Integr Physiol. 2003 Mar;134(3):665-73 - PubMed
  20. J Biol Chem. 2003 May 23;278(21):19095-101 - PubMed
  21. Eur Surg Res. 1998;30(6):385-92 - PubMed
  22. HPB Surg. 1992;5(2):103-14; discussion 114-5 - PubMed
  23. Trends Genet. 2005 Oct;21(10):559-67 - PubMed
  24. Environ Health Perspect. 1993 Dec;101 Suppl 5:67-71 - PubMed
  25. Syst Biol (Stevenage). 2006 Nov;153(6):433-47 - PubMed
  26. Anal Biochem. 1983 Aug;133(1):46-57 - PubMed
  27. FASEB J. 2005 Mar;19(3):440-2 - PubMed
  28. Genomics. 2005 Apr;85(4):425-30 - PubMed
  29. J Mol Cell Cardiol. 2006 Oct;41(4):601-12 - PubMed
  30. J Clin Invest. 2009 Jul;119(7):1880-7 - PubMed
  31. Pharmacol Ther. 1992;53(3):275-354 - PubMed
  32. J Cell Sci. 2007 Oct 15;120(Pt 20):3633-9 - PubMed
  33. J Cell Physiol. 2002 May;191(2):138-44 - PubMed
  34. Mamm Genome. 2007 Sep;18(9):617-26 - PubMed
  35. Curr Opin Genet Dev. 2007 Apr;17(2):157-62 - PubMed
  36. Carcinogenesis. 1988 Sep;9(9):1647-55 - PubMed
  37. J Comput Biol. 2009 Jul;16(7):959-67 - PubMed
  38. Nature. 2010 Oct 7;467(7316):707-10 - PubMed
  39. Nat Rev Mol Cell Biol. 2004 Jan;5(1):45-54 - PubMed
  40. Histochemistry. 1986;84(4-6):308-16 - PubMed
  41. EMBO J. 1990 Aug;9(8):2409-13 - PubMed
  42. Genomics. 2007 Jan;89(1):70-80 - PubMed
  43. PLoS One. 2016 Nov 28;11(11):e0167158 - PubMed
  44. Am J Cardiovasc Pathol. 1995;5(1):27-31 - PubMed
  45. Biotech Histochem. 1993 Jan;68(1):56-63 - PubMed
  46. Hepatology. 1994 May;19(5):1072-8 - PubMed

Publication Types