Dynamic zonation of liver polyploidy
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The liver is a polyploid organ, consisting of hepatocytes with one or two nuclei each containing 2, 4, 8 or more haploid chromosome sets. The dynamic changes in the spatial distributions of polyploid classes across the liver lobule, its repeating anatomical unit, have not been characterized. Identifying these spatial patterns is important for understanding liver homeostatic and regenerative turnover, as well as potential division of labor among ploidy classes. Here, we use single molecule-based tissue imaging to reconstruct the spatial zonation profiles of liver polyploid classes in mice of different ages. We find that liver polyploidy proceeds in spatial waves, advancing more rapidly in the mid-lobule zone compared to the periportal and perivenous zones. We also measure the spatial zonation profiles of S-phase entry at different ages and identify more rapid S-phase entry in the mid-lobule zone at older ages. Our findings reveal fundamental features of liver spatial heterogeneity and highlight their dynamic changes during development and aging.
KeywordsLiver zonation Liver polyploidy Systems biology Single molecule imaging Stem cells
We thank Shanie Landen for valuable comments on the manuscript. S.I. is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics, The Leir Charitable Foundations, Richard Jakubskind Laboratory of Systems Biology, Cymerman-Jakubskind Prize, The Lord Sieff of Brimpton Memorial Fund, The Human Frontiers Science Program, the I-CORE program of the Planning and Budgeting Committee and the Israel Science Foundation, the European Molecular Biology Organization Young Investigator Program and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement number 335122. S.I. is the incumbent of the Philip Harris and Gerald Ronson Career Development Chair.
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