Sun, Tianliang, Cong, Feng, Pikiolek, Monika, Roma, Guglielmo, Orsini, Vanessa, Bergling, Sebastian, Bouwmeester, Antonius, Morelli, Lapo, Hoppe, Philipp, Holwerda, Sjoerd and Lohmann, Felix (2020) The role of AXIN2+ pericentral hepatocytes during liver homeostasis and regeneration. Cell stem cell, na (x). x-x. ISSN na

Abstract

The existence of a specialized tissue stem cell niche, which safeguards liver homeostasis and repair, like AXIN2+ pericentral hepatocytes, is controversial. Using an improved AXIN2 lineage tracing model we confirm the regenerative capacity of intestinal stem cells (ISCs) but contest that pericentral hepatocytes repopulate the liver parenchyma during homeostasis. Likewise, liver regrowth following partial hepatectomy is enabled by proliferation of hepatocytes throughout the liver rather than by the pericentral niche. Periportal hepatocyte injury triggers local repair and auxiliary proliferation throughout all liver zones. DTA-mediated ablation of the AXIN2+ pericentral hepatocytes transiently disrupts this niche which is reestablished by conversion of glutamine synthetase (GS)- hepatocytes, newly juxtaposed to the pericentral vein, to GS+ hepatocytes rather than by proliferation of residual AXIN2+ hepatocytes. Hepatocytes throughout the liver upregulate AXIN2 and LGR5 following injury and contribute to liver regeneration on demand, without zonal dominance of a putative pericentral stem cell niche.

Item Type:	Article
Keywords:	liver stem cell, axin2, lineage tracing,liver regeneation
Date Deposited:	14 Aug 2025 00:45
Last Modified:	14 Aug 2025 00:45
URI:	https://oak.novartis.com/id/eprint/40770