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

被引：121

作者：

Sun, Tianliang ^{[1
]}

Pikiolek, Monika ^{[1
]}

Orsini, Vanessa ^{[1
]}

Bergling, Sebastian ^{[1
]}

Holwerda, Sjoerd ^{[1
]}

Morelli, Lapo ^{[1
]}

Hoppe, Philipp S. ^{[1
]}

Planas-Paz, Lara ^{[1
]}

Yang, Yi ^{[2
]}

Ruffner, Heinz ^{[1
]}

Bouwmeester, Tewis ^{[1
]}

Lohmann, Felix ^{[1
]}

Terracciano, Luigi M. ^{[3
]}

Roma, Guglielmo ^{[1
]}

Cong, Feng ^{[2
]}

Tchorz, Jan S. ^{[1
]}

机构：

[1] Novartis Pharma AG, Novartis Inst BioMed Res, Basel, Switzerland

[2] Novartis Pharma AG, Novartis Inst BioMed Res, Cambridge, MA USA

[3] Univ Hosp Basel, Inst Pathol, Basel, Switzerland

来源：

CELL STEM CELL | 2020年 / 26卷 / 01期

关键词：

BETA-CATENIN; STEM-CELLS; PROGENITOR CELLS; ZONATION; EXPRESSION; APOPTOSIS; RENEWAL;

D O I：

10.1016/j.stem.2019.10.011

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 regenerative potential of intestinal stem cells (ISCs) but find limited roles for pericentral hepatocytes in liver parenchyma homeostasis. Liver regrowth following partial hepatectomy is enabled by proliferation of hepatocytes throughout the liver, rather than by a pericentral population. Periportal hepatocyte injury triggers local repair as well as auxiliary proliferation in all liver zones. DTA-mediated ablation of AXIN2(+) pericentral hepatocytes transiently disrupts this zone, which is reestablished by conversion 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 LGR5 after injury and contribute to liver regeneration on demand, without zonal dominance by a putative pericentral stem cell population.

引用

页码：97 / +

页数：17

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