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研究揭示AXIN2中枢周围肝细胞的功能
作者:小柯机器人 发布时间:2019/12/20 16:35:58

瑞士诺华生物医学研究所Jan S. Tchorz研究组发现,AXIN2+中轴周围肝细胞对肝稳态和再生的贡献有限。相关论文2019年12月19日在线发表在国际学术期刊《细胞—干细胞》上。

通过对BAC转基因小鼠中AXIN2谱系追踪,研究人员证实肠干细胞(ISC)的再生潜能,但在肝稳态中,中轴周围肝细胞的作用有限。肝部分切除后,肝脏的再生是通过肝细胞在整个肝脏中的增殖而不是在中轴周围实现的。周围肝细胞损伤触发所有肝脏区域的局部修复以及辅助增殖。 DTA介导的AXIN2 +中央肝细胞缺失可暂时破坏该区域,但可以通过将中央静脉并置的谷氨酰胺合成酶(GS)-肝细胞转化为GS +肝细胞,以及肝细胞在肝区的补偿性增殖重新建立。这些发现表明,在肝脏损伤后可以通过上调肝细胞AXIN2和LGR5按需促进肝脏再生,而不是由假定的中轴周围干细胞群产生的区域优势。

据悉,科学界对专职肝脏干细胞群体(如AXIN2 +中心肝细胞)是否存在以维持肝稳态和修复一直存在争议。

附:英文原文

Title: AXIN2+ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration

Author: Tianliang Sun, Monika Pikiolek, Vanessa Orsini, Sebastian Bergling, Sjoerd Holwerda, Lapo Morelli, Philipp S. Hoppe, Lara Planas-Paz, Yi Yang, Heinz Ruffner, Tewis Bouwmeester, Felix Lohmann, Luigi M. Terracciano, Guglielmo Roma, Feng Cong, Jan S. Tchorz

Issue&Volume: December 19, 2019

Abstract: The existence of specialized liver stem cell populations, including AXIN2+ pericentral hepatocytes, that safeguard homeostasis and repair has been controversial.Here, using AXIN2 lineage tracing in BAC-transgenic mice, we confirm the regenerativepotential of intestinal stem cells (ISCs) but find limited roles for pericentral hepatocytesin liver parenchyma homeostasis. Liver regrowth following partial hepatectomy is enabledby proliferation of hepatocytes throughout the liver, rather than by a pericentralpopulation. Periportal hepatocyte injury triggers local repair as well as auxiliaryproliferation in all liver zones. DTA-mediated ablation of AXIN2+ pericentral hepatocytes transiently disrupts this zone, which is reestablished byconversion of pericentral vein-juxtaposed glutamine synthetase (GS)– hepatocytes into GS+ hepatocytes and by compensatory proliferation of hepatocytes across liver zones.These findings show hepatocytes throughout the liver can upregulate AXIN2 and LGR5after injury and contribute to liver regeneration on demand, without zonal dominanceby a putative pericentral stem cell population.

DOI: 10.1016/j.stem.2019.10.011

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30432-1

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx