In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration
In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration
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DOI：
10.1016/j.stem.2019.11.014
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发表时间：
2020-01-01
期刊：
影响因子：
23.9
通讯作者：
Grompe, Markus
中科院分区：
文献类型：
--
作者：
Matsumoto, Tomonori;Wakefield, Leslie;Grompe, Markus
损伤后驱动肝再生的细胞群体的身份是深入研究的主题，多倍体肝细胞对器官再生和稳态的贡献尚未得到系统评估。在这里，我们开发了一个报告基因等位基因系统，遗传标记和跟踪多倍体细胞原位。多色多倍体肝细胞在移植后经历倍性降低和随后的再多倍化，为肝细胞倍性输送模型提供了直接证据。标记分离表明，倍性降低很少涉及染色体在体内的误分离。我们还在几种不同的肝损伤模型中追踪了多倍体肝细胞，并在所有情况下发现了强大的增殖。重要的是，在所有研究的损伤模型中均观察到倍性降低。因此，我们得出结论，多倍体肝细胞具有广泛的原位再生能力，并经常在再生反应过程中进行还原性有丝分裂。
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.