Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver
By Bruce Wang, Ludan Zhao, M. Fish, C. Logan, R. Nusse. Nature, 2015
646 citations recorded by the source corpus.
The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2 in mice, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thereby differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes, and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.
Subfields: Hepatology, Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/a10ee56cb96db4cf27c794668d9f8c13f0193545
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Citations in the corpus
- Wnt signaling in development and tissue homeostasis (2018, background): “…experiments using Wnt-target gene reporters have revealed labeled stem cells in several tissues, including the intestine (Barker et al., 2007), the stomach (Barker et al., 2010), the skin (Lim et al., 2013), the liver (Wang et al., 2015) and the mammary gland (van Amerongen et al., 2012).”
- Surrogate Wnt agonists that phenocopy canonical Wnt/β-catenin signaling (2017, neutral): “In the liver, Wnt proteins are expressed around the central vein 23 , and activate a Wnt-driven pericentral gene expression program, such as glutamine synthetase (encoded by Glul in mice, also known as Glns ), in hepatocytes immediately adjacent to the source, resulting in metabolic zonation 24 .”
- Wnt/ b -Catenin Signaling, Disease, and Emerging Therapeutic Modalities (2017, background): “, 2013), and the pericentral region of liver lobules (Wang et al., 2015).”
- Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids. (2018, neutral): “This comes as no surprise given that strong Wnt/R-spondin signaling has been implied in hepatocyte proliferation in vivo (Planas-Paz et al., 2016; Wang et al., 2015).”