Kreutz Clemens, MacNelly Sabine, Follo Marie, Wäldin Astrid, Binninger-Lacour Petra, Timmer Jens, Bartolomé-Rodríguez María M
Faculty of Mathematics and Physics, Institute of Physics, University of Freiburg, Freiburg, Germany.
Center for Systems Biology (ZBSA), University of Freiburg, Freiburg, Germany.
Front Physiol. 2017 Oct 31;8:862. doi: 10.3389/fphys.2017.00862. eCollection 2017.
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.
多倍体，即细胞中存在不止一对染色体，是哺乳动物肝细胞的一个众所周知的特征。多倍体肝细胞既可以是具有单个多倍体核的细胞，也可以是具有二倍体甚至多倍体核的多核细胞。在本研究中，我们通过计算DNA含量和每个细胞的核数量来评估小鼠肝脏中的多倍体程度。我们证明，与具有多倍体核的细胞相比，具有二倍体核的小鼠肝细胞具有不同的代谢特征。除了包括代谢和信号化合物在内的强烈差异基因表达外，我们还发现核多倍体细胞的胰岛素结合能力大幅下降。我们的观察结果与核倍性有关，而与细胞内的总倍性无关。因此，我们认为核的倍性是肝细胞的一个新的多样性因素，并推测具有多倍体核的肝细胞可能具有与单核肝细胞不同的生物学功能。这种多样性独立于与细胞沿肝门-中央肝轴位置相关的众所周知的异质性。
