The Ploidy Conveyor of Mature Hepatocytes As a Source of Genetic Variation

Overview

Journal Nature

Specialty Science

Date 2010 Sep 24

PMID 20861837

Citations 258

Authors

Andrew W Duncan

Matthew H Taylor

Raymond D Hickey

Amy E Hanlon Newell

Michelle L Lenzi

Susan B Olson

Milton J Finegold

Markus Grompe

Affiliations

Soon will be listed here.

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.

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