The ploidy conveyor of mature hepatocytes as a source of genetic variation

Andrew W. Duncan, Matthew Taylor, Raymond D. Hickey, Amy E. Hanlon Newell, Michelle L. Lenzi, Susan Olson, Milton J. Finegold, Markus Grompe

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Mononucleated and binucleated polyploid hepatocytes (4n, 8n, 16n and higher) are found in all mammalian species, but the functional significance of this conserved phenomenon remains unknown. Polyploidization occurs through failed cytokinesis, begins at weaning in rodents and increases with age. Previously, we demonstrated that the opposite event, ploidy reversal, also occurs in polyploid hepatocytes generated by artificial cell fusion. This raised the possibility that somatic reductive mitoses can also happen in normal hepatocytes. Here we show that multipolar mitotic spindles form frequently in mouse polyploid hepatocytes and can result in one-step ploidy reversal to generate offspring with halved chromosome content. Proliferating hepatocytes produce a highly diverse population of daughter cells with multiple numerical chromosome imbalances as well as uniparental origins. Our findings support a dynamic model of hepatocyte polyploidization, ploidy reversal and aneuploidy, a phenomenon that we term the ploidy conveyor. We propose that this mechanism evolved to generate genetic diversity and permits adaptation of hepatocytes to xenobiotic or nutritional injury.

Original languageEnglish (US)
Pages (from-to)707-710
Number of pages4
JournalNature
Volume467
Issue number7316
DOIs
StatePublished - Oct 7 2010

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Ploidies
Hepatocytes
Polyploidy
Chromosomes
Artificial Cells
Spindle Apparatus
Cytokinesis
Cell Fusion
Aneuploidy
Xenobiotics
Weaning
Mitosis
Rodentia
Wounds and Injuries
Population

ASJC Scopus subject areas

  • General

Cite this

The ploidy conveyor of mature hepatocytes as a source of genetic variation. / Duncan, Andrew W.; Taylor, Matthew; Hickey, Raymond D.; Hanlon Newell, Amy E.; Lenzi, Michelle L.; Olson, Susan; Finegold, Milton J.; Grompe, Markus.

In: Nature, Vol. 467, No. 7316, 07.10.2010, p. 707-710.

Research output: Contribution to journalArticle

Duncan, AW, Taylor, M, Hickey, RD, Hanlon Newell, AE, Lenzi, ML, Olson, S, Finegold, MJ & Grompe, M 2010, 'The ploidy conveyor of mature hepatocytes as a source of genetic variation', Nature, vol. 467, no. 7316, pp. 707-710. https://doi.org/10.1038/nature09414
Duncan AW, Taylor M, Hickey RD, Hanlon Newell AE, Lenzi ML, Olson S et al. The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature. 2010 Oct 7;467(7316):707-710. https://doi.org/10.1038/nature09414
Duncan, Andrew W. ; Taylor, Matthew ; Hickey, Raymond D. ; Hanlon Newell, Amy E. ; Lenzi, Michelle L. ; Olson, Susan ; Finegold, Milton J. ; Grompe, Markus. / The ploidy conveyor of mature hepatocytes as a source of genetic variation. In: Nature. 2010 ; Vol. 467, No. 7316. pp. 707-710.
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