In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration.,Cell Stem Cell

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In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-12-19 , DOI: 10.1016/j.stem.2019.11.014
Tomonori Matsumoto ₁ , Leslie Wakefield ₂ , Branden David Tarlow ₃ , Markus Grompe ₂

Affiliation

The identity of cellular populations that drive liver regeneration after injury is the subject of intense study, and the contributions of polyploid hepatocytes to organ regeneration and homeostasis have not been systematically assessed. Here, we developed a multicolor reporter allele system to genetically label and trace polyploid cells in situ. Multicolored polyploid hepatocytes undergo ploidy reduction and subsequent re-polyploidization after transplantation, providing direct evidence of the hepatocyte ploidy conveyor model. Marker segregation revealed that ploidy reduction rarely involves chromosome missegregation in vivo. We also traced polyploid hepatocytes in several different liver injury models and found robust proliferation in all settings. Importantly, ploidy reduction was seen in all injury models studied. We therefore conclude that polyploid hepatocytes have extensive regenerative capacity in situ and routinely undergo reductive mitoses during regenerative responses.

中文翻译：

多倍体肝细胞的体内谱系追踪揭示了肝再生过程中的广泛增殖。

损伤后驱动肝脏再生的细胞群的身份是一项深入研究的主题，多倍体肝细胞对器官再生和体内稳态的贡献尚未得到系统的评估。在这里，我们开发了一种多色报告基因等位基因系统，可以在基因上原位标记和追踪多倍体细胞。多彩多姿的多倍体肝细胞在移植后经历了倍性减少和随后的多倍体化，从而提供了肝细胞倍性转运模型的直接证据。标记分离显示，倍性减少很少涉及体内染色体错配。我们还在几种不同的肝损伤模型中追踪了多倍体肝细胞，并发现在所有情况下均具有强大的增殖能力。重要的是，在所有研究的损伤模型中均观察到倍性减少。

更新日期：2019-12-19

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