美国俄勒冈健康与科学大学Markus Grompe研究团队发现多倍体肝细胞的体内谱系示踪显示肝再生过程中的广泛增殖。该研究2019年12月19日在线发表于国际学术期刊《细胞—干细胞》。

研究人员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。 多色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变模型的直接证据。标记分离显示，倍性减少很少涉及体内染色体错配。他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能稳定增殖。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，他们得出结论，多倍体肝细胞具有广泛的原位再生能力，并且在再生反应过程中通常经历还原性有丝分裂。

研究人员表示，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，而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。

附：英文原文

Title: In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration

Author: Tomonori Matsumoto, Leslie Wakefield, Branden David Tarlow, Markus Grompe

Issue&Volume: December 19, 2019

Abstract: The identity of cellular populations that drive liver regeneration after injury isthe subject of intense study, and the contributions of polyploid hepatocytes to organregeneration and homeostasis have not been systematically assessed. Here, we developeda multicolor reporter allele system to genetically label and trace polyploid cellsin situ. Multicolored polyploid hepatocytes undergo ploidy reduction and subsequent re-polyploidizationafter transplantation, providing direct evidence of the hepatocyte ploidy conveyormodel. Marker segregation revealed that ploidy reduction rarely involves chromosomemissegregation in vivo. We also traced polyploid hepatocytes in several different liver injury models andfound robust proliferation in all settings. Importantly, ploidy reduction was seenin all injury models studied. We therefore conclude that polyploid hepatocytes haveextensive regenerative capacity in situ and routinely undergo reductive mitoses during regenerative responses.

DOI: 10.1016/j.stem.2019.11.014

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30469-2