Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver
Open accessAbstract
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.
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Recent studies have demonstrated that hepatocytes are primarily maintained by the proliferation of pre-existing hepatocytes during liver homeostasis and regeneration.
“recent studies have demonstrated that hepatocytes are primarily maintained by the proliferation of pre-existing hepatocytes during liver homeostasis and regeneration14–19”
From Multimodal decoding of human liver regeneration (2024) · cites this paper as [19]
The Abstract reports that earlier lineage-tracing studies found new hepatocytes arise from pre-existing hepatocytes during homeostatic renewal. This paper’s own findings concern a self-renewing pericentral population in the uninjured liver; its Discussion does not establish that proliferation of pre-existing hepatocytes primarily maintains hepatocytes during regeneration. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn mouse and human liver, Wnt ligands are produced by endothelial cells of central vein branches and nearby sinusoids.
“In the mouse and human liver, Wnt ligands are produced by endothelial cells of the central vein branches and the nearby sinusoids (17–19)”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [17]
The Discussion reports Wnt9b expression in central-vein endothelial cells and Wnt2 expression in both central-vein and sinusoidal endothelial cells. The experiments described are in mice; our copy does not establish the same finding in human liver. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn mouse and human liver, Wnt ligands are produced by endothelial cells of central vein branches and nearby sinusoids, creating a zonated expression pattern of Wnt target genes and key metabolic enzymes in pericentral hepatocytes.
“In the mouse and human liver, Wnt ligands are produced by endothelial cells of the central vein branches and the nearby sinusoids (McEnerney et al. 2017;Wang et al. 2015;Zhao et al. 2019), creating a zonated expression pattern of Wnt target genes and key metabolic enzymes in pericentral hepatocytes (Halpern et al. 2017).”
From Hepatocyte Cell Cycle Progression Depends on a Transcriptional Repressor Cascade Downstream of Wnt Signaling (2021) · cites this paper as Wang et al. 2015
The “Central vein endothelium acts as a Wnt-producing niche” section reports Wnt2 and Wnt9b production by central-vein endothelial cells, and the Discussion specifies that Wnt2 is also expressed in sinusoidal endothelial cells. The experiments described are in mice; these passages do not establish the claim for human liver. The later zonation clause is attributed to a different citation, not to this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTbx3 is expressed in a zonated pattern during postnatal liver growth.
“The transcriptional repressor Tbx3, a gene required for embryonic liver development (Khan et al. 2020;Ludtke et al. 2009;Suzuki et al. 2008), is also expressed in a zonated pattern during postnatal liver growth (fig.S1A) (Wang et al. 2015;Zhao et al. 2019).”
From Hepatocyte Cell Cycle Progression Depends on a Transcriptional Repressor Cascade Downstream of Wnt Signaling (2021) · cites this paper as Wang et al. 2015
The “Axin2+ cells self-renew” section reports that Tbx3 expression is confined to a single layer of pericentral cells, supporting zonated expression. The Methods identify the mice used for the Tbx3 in situ images as eight-week-old animals; the paper studies adult liver homeostasis, not expression during postnatal liver growth specifically. (LLM, conf=0.85)
Experimental — accuracy not yet measuredTbx3 is among the genes highly expressed in the pericentral zone.
“Among the genes highly expressed in the pericentral zone is the transcriptional repressor Tbx3 (17, 19).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [17]
Lineage-tracing data have shown that hepatocytes in different zones can adopt the gene expression programme of the new zone they reside in.
“Additionally, lineage-tracing data have shown that hepatocytes in the different zones can adopt the gene expression programme of the new zone they reside in.49,60,84,86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [49]
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Cites
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository
Edgar, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.207 · Cited by 13,288 · see citing works
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668 · see citing works
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687 · see citing works
Organoid Models and Applications in Biomedical Research
Xinaris, C., Brizi, V., & Remuzzi, G. (2015) · The Nephron journals/Nephron journals · doi:10.1159/000433566 · Cited by 3,517 · see citing works
Differential analysis of gene regulation at transcript resolution with RNA-seq
Trapnell, C., Hendrickson, D. G., Sauvageau, M., Goff, L., Rinn, J. L., & Pachter, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2450 · Cited by 3,492 · see citing works
A global double-fluorescent Cre reporter mouse
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L., & Luo, L. (2007) · genesis · doi:10.1002/dvg.20335 · Cited by 3,491 · see citing works
Goecks, J., Nekrutenko, A., Taylor, J., & The Galaxy Team (2010) · Genome biology · doi:10.1186/gb-2010-11-8-r86 · Cited by 3,437 · see citing works
(2012) · doi:10.1016/j.jmoldx.2011.08.002 · Cited by 2,567 · see citing works
The advantages and disadvantages of being polyploid
Comai, L. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1711 · Cited by 2,308 · see citing works
Defining the Epithelial Stem Cell Niche in Skin
Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W. E., Rendl, M., & Fuchs, E. (2004) · Science · doi:10.1126/science.1092436 · Cited by 2,031 · see citing works
In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
Huch, M., Dorrell, C., Boj, S. F., van Es, J. H., Li, V. S. W., van de Wetering, M., Sato, T., Hamer, K., Sasaki, N., Finegold, M. J., et al. (2013) · Nature · doi:10.1038/nature11826 · Cited by 1,555 · see citing works
An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control
Clevers, H. C., Loh, K. M., & Nusse, R. (2014) · Science · doi:10.1126/science.1248012 · Cited by 1,351 · see citing works
Self-citationLustig, B., Jerchow, B., Sachs, M., Weiler, S., Pietsch, T., Karsten, U., van de Wetering, M., Clevers, H., Schlag, P., Birchmeier, W., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1184-1193.2002 · Cited by 1,198 · see citing works
The adult Drosophila posterior midgut is maintained by pluripotent stem cells
Ohlstein, B., & Spradling, A. C. (2005) · Nature · doi:10.1038/nature04333 · Cited by 1,089 · see citing works
DasGupta, R., & Fuchs, E. V. (1999) · Development · doi:10.1242/dev.126.20.4557 · Cited by 995 · see citing works
Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration
Ding, B., Nolan, D. J., Butler, J. M., James, D., Babazadeh, A. O., Rosenwaks, Z., Mittal, V., Kobayashi, H., Shido, K., Lyden, D. C., et al. (2010) · Nature · doi:10.1038/nature09493 · Cited by 837 · see citing works
Bänziger, C., Soldini, D., Schütt, C., Zipperlen, P., Hausmann, G., & Basler, K. (2006) · Cell · doi:10.1016/j.cell.2006.02.049 · Cited by 764 · see citing works
Zonation of parenchymal and nonparenchymal metabolism in liver.
Jungermann, K., & Keitzmann, T. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nu.16.070196.001143 · Cited by 589 · see citing works
Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming
Miyajima, A., Tanaka, M., & Itoh, T. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.010 · Cited by 570 · see citing works
Apc Tumor Suppressor Gene Is the “Zonation-Keeper” of Mouse Liver
Benhamouche, S., Decaens, T., Godard, C., Chambrey, R., Rickman, D. S., Moinard, C., Vasseur-Cognet, M., Kuo, C. J., Kahn, A., Perret, C., et al. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.03.015 · Cited by 543 · see citing works
The ploidy conveyor of mature hepatocytes as a source of genetic variation
Duncan, A. W., Taylor, M. H., Hickey, R. D., Hanlon Newell, A. E., Lenzi, M. L., Olson, S. B., Finegold, M. J., & Grompe, M. (2010) · Nature · doi:10.1038/nature09414 · Cited by 525 · see citing works
van Amerongen, R., Bowman, A. N., & Nusse, R. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.05.023 · Cited by 446 · see citing works
Self-citationFate tracing of mature hepatocytes in mouse liver homeostasis and regeneration
Malato, Y., Naqvi, S., Schürmann, N., Ng, R., Wang, B., Zape, J., Kay, M. A., Grimm, D., & Willenbring, H. (2011) · Journal of Clinical Investigation · doi:10.1172/jci59261 · Cited by 434 · see citing works
Self-citationAdult Hepatocytes Are Generated by Self-Duplication Rather than Stem Cell Differentiation
Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E., & Stanger, B. Z. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.06.003 · Cited by 426 · see citing works
New targets of β-catenin signaling in the liver are involved in the glutamine metabolism
Cadoret, A., Ovejero, C., Terris, B., Souil, E., Lévy, L., Lamers, W. H., Kitajewski, J., Kahn, A., & Perret, C. (2002) · Oncogene · doi:10.1038/sj.onc.1206118 · Cited by 412 · see citing works
Zeng, Y. A., & Nusse, R. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.03.020 · Cited by 398 · see citing works
Self-citationKreamer, B. L., Staecker, J. L., Sawada, N., Sattler, G. L., Hsia, M. T. S., & Pitot, H. C. (1986) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02623304 · Cited by 383 · see citing works
Interfollicular Epidermal Stem Cells Self-Renew via Autocrine Wnt Signaling
Lim, X., Tan, S. H., Koh, W. L. C., Chau, R. M. W., Yan, K. S., Kuo, C. J., van Amerongen, R., Klein, A. M., & Nusse, R. (2013) · Science · doi:10.1126/science.1239730 · Cited by 342 · see citing works
Self-citationGenetics of hepatocellular tumors
Laurent‐Puig, P., & Zucman‐Rossi, J. (2006) · Oncogene · doi:10.1038/sj.onc.1209547 · Cited by 317 · see citing works
Liver Cell Polyploidization: A Pivotal Role for Binuclear Hepatocytes
Guidotti, J.-E., Brégerie, O., Robert, A., Debey, P., Brechot, C., & Desdouets, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300982200 · Cited by 315 · see citing works
Mitotic and mitogenic Wnt signalling
Niehrs, C., & Acebron, S. P. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.124 · Cited by 305 · see citing works
Tbx3 improves the germ-line competency of induced pluripotent stem cells
Han, J., Yuan, P., Yang, H., Zhang, J., Soh, B. S., Li, P., Lim, S. L., Cao, S., Tay, J., Orlov, Y. L., et al. (2010) · Nature · doi:10.1038/nature08735 · Cited by 285 · see citing works
Wang, R., Ferrell, L. D., Faouzi, S., Maher, J. J., & Bishop, J. M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.1023 · Cited by 281 · see citing works
Zajicek, G., Oren, R., & Weinreb, M. M. (1985) · Liver International · doi:10.1111/j.1600-0676.1985.tb00252.x · Cited by 273 · see citing works
VE‐cadherin‐CreER T2 transgenic mouse: A model for inducible recombination in the endothelium
Monvoisin, A., Alva, J. A., Hofmann, J. J., Zovein, A. C., Lane, T. F., & Iruela‐Arispe, M. L. (2006) · Developmental Dynamics · doi:10.1002/dvdy.20982 · Cited by 255 · see citing works
Differential gene expression in periportal and perivenous mouse hepatocytes
Braeuning, A., Ittrich, C., Köhle, C., Hailfinger, S., Bonin, M., Buchmann, A., & Schwarz, M. (2006) · The FEBS Journal · doi:10.1111/j.1742-4658.2006.05503.x · Cited by 240 · see citing works
Sigal, S. H., Rajvanshi, P., Gorla, G. R., Sokhi, R. P., Saxena, R., Gebhard, D. R., Reid, L. M., & Gupta, S. K. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.5.g1260 · Cited by 230 · see citing works
Distinct pathways of genomic progression to benign and malignant tumors of the liver
Tward, A. D., Jones, K. D., Yant, S. R., Cheung, S., Fan, S. T., Chen, X., Kay, M. A., Wang, R., & Bishop, J. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706578104 · Cited by 217 · see citing works
Tan, X., Yuan, Y., Zeng, G., Apte, U., Thompson, M. D., Cieply, B., Stolz, D. B., Michalopoulos, G. K., Kaestner, K. H., & Monga, S. P. S. (2008) · Hepatology · doi:10.1002/hep.22225 · Cited by 202 · see citing works
Limiting the Proliferation of Polyploid Cells
Ganem, N. J., & Pellman, D. S. (2007) · Cell · doi:10.1016/j.cell.2007.10.024 · Cited by 174 · see citing works
Generation of mice with a conditional null allele for Wntless
Carpenter, A. C., Rao, S., Wells, J. M., Campbell, K., & Lang, R. A. (2010) · genesis · doi:10.1002/dvg.20651 · Cited by 148 · see citing works
Suzuki, A., Sekiya, S., Büscher, D., Izpisúa Belmonte, J. C., & Taniguchi, H. (2008) · Development · doi:10.1242/dev.016634 · Cited by 136 · cited 2× · see citing works
“The stem cell marker Tbx3 is expressed widely in early liver hepatoblasts and is important for hepatoblast proliferation and initiation of hepatocyte differentiation[19, 37].”
BackgroundVijayakumar, S., Liu, G., Rus, I. A., Yao, S., Chen, Y., Akiri, G., Grumolato, L., & Aaronson, S. A. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.03.010 · Cited by 128 · see citing works
Cell proliferation and renewal of normal hepatocytes and bile duct cells in adult mouse liver
Magami, Y., Azuma, T., Inokuchi, H., Kokuno, S., Moriyasu, F., Kawai, K., & Hattori, T. (2002) · Liver International · doi:10.1034/j.1600-0676.2002.01702.x · Cited by 124 · see citing works
Lüdtke, T. H. ‐., Christoffels, V. M., Petry, M., & Kispert, A. (2009) · Hepatology · doi:10.1002/hep.22700 · Cited by 117 · see citing works
Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis
Schwarze, P. E., Pettersen, E. O., Shoaib, M. C., & Seglen, P. O. (1984) · Carcinogenesis · doi:10.1093/carcin/5.10.1267 · Cited by 95 · see citing works
Impaired neural development caused by inducible expression of Axin in transgenic mice
Yu, H. I., Liu, B., Costantini, F. D., & Hsu, W. (2006) · Mechanisms of Development · doi:10.1016/j.mod.2006.10.002 · Cited by 60 · see citing works
Moreira, P. I., Custódio, J. B. A., NUNES, E., Moreno, A. J., Seiça, R. M. F., Oliveira, C. R., & Santos, M. S. (2007) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2007.02.006 · Cited by 24 · see citing works
Emergence of a population of small diploid hepatocytes during hepatocarcinogenesis
Schwarze, P. E., Pettersen, E. P., Shoaib, M. C., & Seglen, P. O. (1985) · Food and Chemical Toxicology · doi:10.1016/0278-6915(85)90308-4 · Cited by 13 · see citing works
Streaming liver VII: DNA turnover in acinus zone‐3
Zajicek, G., & Schwartz‐Arad, D. (1990) · Liver International · doi:10.1111/j.1600-0676.1990.tb00448.x · Cited by 6 · see citing works
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Nusse, R., & Clevers, H. (2017) · Cell · doi:10.1016/j.cell.2017.05.016 · Cited by 4,342 · see citing works
Self-citationLiver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis
Sia, D., Villanueva, A., Friedman, S., & Llovet, J. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.11.048 · Cited by 1,051 · see citing works
A human liver cell atlas reveals heterogeneity and epithelial progenitors
Aizarani, N., Saviano, A., Sagar, Mailly, L., Durand, S., Herman, J. S., Pessaux, P., Baumert, T. F., & Grün, D. (2019) · Nature · doi:10.1038/s41586-019-1373-2 · Cited by 1,147 · see citing works
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver
Halpern, K. B., Shenhav, R., Matcovitch-Natan, O., Tóth, B., Lemze, D., Golan, M., Massasa, E. E., Baydatch, S., Landen, S., Moor, A. E., et al. (2017) · Nature · doi:10.1038/nature21065 · Cited by 1,059 · see citing works
Liver regeneration: biological and pathological mechanisms and implications
Michalopoulos, G. K., & Bhushan, B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0342-4 · Cited by 998 · see citing works
Angiocrine functions of organ-specific endothelial cells
Rafii, S., Butler, J. M., & Ding, B. (2016) · Nature · doi:10.1038/nature17040 · Cited by 948 · see citing works
Finn, J. D., Smith, A. R., Patel, M. C., Shaw, L., Youniss, M. R., van Heteren, J., Dirstine, T., Ciullo, C., Lescarbeau, R., Seitzer, J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.014 · Cited by 878 · see citing works
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Hu, H., Gehart, H., Artegiani, B., LÖpez-Iglesias, C., Dekkers, F., Basak, O., van Es, J., Chuva de Sousa Lopes, S. M., Begthel, H., Korving, J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.013 · Cited by 837 · see citing works
Wnt signaling in development and tissue homeostasis
Steinhart, Z., & Angers, S. (2018) · Development · doi:10.1242/dev.146589 · Cited by 821 · see citing works
AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control
González, A., Hall, M. N., Lin, S.-C., & Hardie, D. G. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.015 · Cited by 797 · see citing works
Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology
Augustin, H. G., & Koh, G. Y. (2017) · Science · doi:10.1126/science.aal2379 · Cited by 762 · see citing works
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Karin, M., & Clevers, H. (2016) · Nature · doi:10.1038/nature17039 · Cited by 767 · see citing works
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Potente, M., & Mäkinen, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.36 · Cited by 653 · see citing works
Wnt–β-catenin signalling in liver development, health and disease
Perugorria, M. J., Olaizola, P., Labiano, I., Esparza-Baquer, A., Marzioni, M., Marı́n, J. J. G., Bujanda, L., & Bañales, J. M. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0075-9 · Cited by 606 · see citing works
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Raven, A., Lu, W.-Y., Man, T. Y., Ferreira-Gonzalez, S., O’Duibhir, E., Dwyer, B. J., Thomson, J. P., Meehan, R. R., Bogorad, R., Koteliansky, V., et al. (2017) · Nature · doi:10.1038/nature23015 · Cited by 533 · see citing works
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Mason, W. S., Gill, U. S., Litwin, S., Zhou, Y., Peri, S., Pop, O. T., Hong, M. L. W., Naik, S., Quaglia, A., Bertoletti, A., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.07.012 · Cited by 449 · see citing works
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Janda, C. Y., Dang, L. T., You, C., Chang, J., de Lau, W., Zhong, Z. A., Yan, K. S., Marecic, O., Siepe, D., Li, X., et al. (2017) · Nature · doi:10.1038/nature22306 · Cited by 403 · see citing works
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Rappez, L., Stadler, M., Triana, S., Gathungu, R., Ovchinnikova, K., Phapale, P., Heikenwalder, M., & Alexandrov, T. (2021) · Nature Methods · doi:10.1038/s41592-021-01198-0 · Cited by 320 · see citing works
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Halpern, K. B., Shenhav, R., Massalha, H., Toth, B., Egozi, A., Massasa, E. E., Medgalia, C., David, E., Giladi, A., Moor, A. E., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4231 · Cited by 368 · see citing works
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Planas-Paz, L., Orsini, V., Boulter, L., Calabrese, D., Pikiolek, M., Nigsch, F., Xie, Y., Roma, G., Donovan, A., Marti, P., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3337 · Cited by 359 · see citing works
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Tammela, T., Rivera, F. J. S., Cetinbas, N. M., Wu, K., Joshi, N. S., Helenius, K. P., Park, Y., Azimi, R., Kerper, N. R., Wesselhoeft, R. A., et al. (2017) · Nature · doi:10.1038/nature22334 · Cited by 338 · see citing works
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Wei, Y., Wang, Y. G., Jia, Y., Li, L., Yoon, J., Zhang, S., Wang, Z., Zhang, Y., Zhu, M., Sharma, T., et al. (2021) · Science · doi:10.1126/science.abb1625 · Cited by 292 · see citing works
Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease
Wu, X., Fan, X., Miyata, T., Kim, A., Cajigas-Du Ross, C. K., Ray, S., Huang, E., Taiwo, M., Arya, R., Wu, J., et al. (2023) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031521-030435 · Cited by 289 · see citing works
Saviano, A., Henderson, N. C., & Baumert, T. F. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.06.004 · Cited by 269 · see citing works
Liu, Y., Tao, S., Liao, L., Li, Y., Li, H., Li, Z., Lin, L., Wan, X., Yang, X., & Chen, L. (2020) · Nature Communications · doi:10.1038/s41467-019-14190-2 · Cited by 265 · see citing works
Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair
He, L., Pu, W., Liu, X., Zhang, Z., Han, M., Li, Y., Huang, X., Han, X., Li, Y., Liu, K., et al. (2021) · Science · doi:10.1126/science.abc4346 · Cited by 261 · see citing works
Katsuda, T., Kawamata, M., Hagiwara, K., Takahashi, R.-U., Yamamoto, Y., Camargo, F. D., & Ochiya, T. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.10.007 · Cited by 260 · see citing works
The endothelium–bone axis in development, homeostasis and bone and joint disease
Tuckermann, J., & Adams, R. H. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-021-00682-3 · Cited by 258 · see citing works
Lazzeri, E., Angelotti, M. L., Peired, A. J., Conte, C., Marschner, J. A., Maggi, L., Mazzinghi, B., Lombardi, D., Melica, M. E., Nardi, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03753-4 · Cited by 258 · see citing works
Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis
Ramachandran, P., Matchett, K. P., Dobie, R., Wilson-Kanamori, J. R., & Henderson, N. C. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0304-x · Cited by 253 · see citing works
Comparative regenerative mechanisms across different mammalian tissues
Iismaa, S. E., Kaidonis, X., Nicks, A. M., Bogush, N., Kikuchi, K., Naqvi, N., Harvey, R. P., Husain, A., & Graham, R. M. (2018) · npj Regenerative Medicine · doi:10.1038/s41536-018-0044-5 · Cited by 256 · see citing works
In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity
Zhang, K., Zhang, L., Liu, W., Ma, X., Cen, J., Sun, Z., Wang, C., Feng, S., Zhang, Z., Yue, L., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.10.018 · Cited by 252 · see citing works
Somatic Mutations Increase Hepatic Clonal Fitness and Regeneration in Chronic Liver Disease
Zhu, M., Lu, T., Jia, Y., Luo, X., Gopal, P., Li, L., Odewole, M., Renteria, V., Singal, A. G., Jang, Y., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.026 · Cited by 250 · see citing works
Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury
Lin, S., Nascimento, E. M., Gajera, C. R., Chen, L., Neuhöfer, P., Garbuzov, A., Wang, S., & Artandi, S. E. (2018) · Nature · doi:10.1038/s41586-018-0004-7 · Cited by 241 · see citing works
Wnt signalling: conquering complexity
Wiese, K. E., Nusse, R., & van Amerongen, R. (2018) · Development · doi:10.1242/dev.165902 · Cited by 238 · see citing works
Self-citationBroad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration
Chen, F., Jimenez, R. J., Sharma, K., Luu, H. Y., Hsu, B. Y., Ravindranathan, A., Stohr, B. A., & Willenbring, H. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.11.001 · Cited by 236 · see citing works
Defining Adult Stem Cells by Function, not by Phenotype
Clevers, H. C., & Watt, F. M. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012341 · Cited by 226 · see citing works
Rare Pulmonary Neuroendocrine Cells Are Stem Cells Regulated by Rb, p53, and Notch
Ouadah, Y., Rojas, E., Riordan, D. P., Capostagno, S., Kuo, C. S., & Krasnow, M. A. (2019) · Cell · doi:10.1016/j.cell.2019.09.010 · Cited by 219 · see citing works
Mechano-modulatory synthetic niches for liver organoid derivation
Sorrentino, G., Rezakhani, S., Yildiz, E., Nuciforo, S., Heim, M. H., Lutolf, M. P., & Schoonjans, K. (2020) · Nature Communications · doi:10.1038/s41467-020-17161-0 · Cited by 224 · see citing works
The spatiotemporal program of zonal liver regeneration following acute injury
Ben-Moshe, S., Veg, T., Manco, R., Dan, S., Papinutti, D., Lifshitz, A., Kolodziejczyk, A. A., Bahar Halpern, K., Elinav, E., & Itzkovitz, S. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.04.008 · Cited by 224 · see citing works
Su, T., Yang, Y., Lai, S., Jeong, J., Jung, Y., McConnell, M., Utsumi, T., & Iwakiri, Y. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.12.007 · Cited by 220 · see citing works
The balancing act of the liver: tissue regeneration versus fibrosis
Cordero-Espinoza, L., & Huch, M. (2018) · Journal of Clinical Investigation · doi:10.1172/jci93562 · Cited by 220 · see citing works
Planas-Paz, L., Sun, T., Pikiolek, M., Cochran, N. R., Bergling, S., Orsini, V., Yang, Z., Sigoillot, F., Jetzer, J., Syed, M., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.005 · Cited by 216 · see citing works
Spatial sorting enables comprehensive characterization of liver zonation
Ben-Moshe, S., Shapira, Y., Moor, A. E., Halpern, K. B., & Itzkovitz, S. (2019) · doi:10.1101/529784 · Cited by 205 · see citing works
Spatial sorting enables comprehensive characterization of liver zonation
Ben-Moshe, S., Shapira, Y., Moor, A. E., Manco, R., Veg, T., Bahar Halpern, K., & Itzkovitz, S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0109-9 · Cited by 205 · see citing works
The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation
Rocha, A. S., Vidal, V., Mertz, M., Kendall, T. J., Charlet, A., Okamoto, H., & Schedl, A. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.049 · Cited by 194 · see citing works
Matsumoto, T., Wakefield, L., Tarlow, B. D., & Grompe, M. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.11.014 · Cited by 194 · see citing works
The Polyploid State Plays a Tumor-Suppressive Role in the Liver
Zhang, S., Zhou, K., Luo, X., Li, L., Tu, H.-C., Sehgal, A., Nguyen, L. H., Zhang, Y., Gopal, P., Tarlow, B. D., et al. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.010 · Cited by 180 · see citing works
Defining Adult Stem Cell Function at Its Simplest: The Ability to Replace Lost Cells through Mitosis
Post, Y., & Clevers, H. C. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.07.002 · Cited by 176 · see citing works
Spatial single-cell mass spectrometry defines zonation of the hepatocyte proteome
Rosenberger, F. A., Thielert, M., Strauss, M. T., Schweizer, L., Ammar, C., Mädler, S. C., Metousis, A., Skowronek, P., Wahle, M., Madden, K., et al. (2023) · Nature Methods · doi:10.1038/s41592-023-02007-6 · Cited by 176 · see citing works
Stem cells versus plasticity in liver and pancreas regeneration
Kopp, J. L., Grompe, M., & Sander, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3309 · Cited by 176 · see citing works
Amino acid metabolism, transport and signalling in the liver revisited.
Paulusma, C., Lamers, W., Bröer, S., & van de Graaf, S. V. D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115074 · Cited by 162 · see citing works
Understanding Liver Regeneration
Gilgenkrantz, H., & Collin de l'Hortet, A. (2018) · The American Journal of Pathology · doi:10.1016/j.ajpath.2018.03.008 · Cited by 171 · see citing works
Regulation of Hematopoiesis and Osteogenesis by Blood Vessel–Derived Signals
Ramasamy, S. K., Kusumbe, A. P., Itkin, T., Gur‐Cohen, S., Lapidot, T., & Adams, R. H. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-124936 · Cited by 169 · see citing works
Winkler, M., Staniczek, T., Kürschner, S. W., Schmid, C. D., Schönhaber, H., Cordero, J., Kessler, L., Mathes, A., Sticht, C., Neßling, M., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.08.033 · Cited by 170 · see citing works
Diverse mechanisms for endogenous regeneration and repair in mammalian organs
Wells, J. M., & Watt, F. M. (2018) · Nature · doi:10.1038/s41586-018-0073-7 · Cited by 169 · see citing works
Cell Plasticity in Liver Regeneration
Li, W., Li, L., & Hui, L. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.01.007 · Cited by 167 · see citing works
Paris, J., & Henderson, N. C. (2022) · Hepatology · doi:10.1002/hep.32408 · Cited by 167 · see citing works
AXIN2+ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration
Sun, T., Pikiolek, M., Orsini, V., Bergling, S., Holwerda, S., Morelli, L., Hoppe, P. S., Planas-Paz, L., Yang, Y., Ruffner, H., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.10.011 · Cited by 166 · see citing works
Liver Zonation – Revisiting Old Questions With New Technologies
Cunningham, R. P., & Porat‐Shliom, N. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.732929 · Cited by 166 · see citing works
Takase, H. M., & Nusse, R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1601461113 · Cited by 165 · see citing works
Self-citationOrganoids to model liver disease
Nuciforo, S., & Heim, M. H. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2020.100198 · Cited by 164 · see citing works
Lanzoni, G., Cardinale, V., & Carpino, G. (2015) · Hepatology · doi:10.1002/hep.28326 · Cited by 163 · see citing works
Géraud, C., Reiners-Koch, P.-S., Zierow, J., Klapproth, K., Busch, K., Olsavszky, V., Leibing, T., Demory, A., Ulbrich, F., Diett, M., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90086 · Cited by 164 · see citing works
Recent Advances in Lgr5 + Stem Cell Research
Leung, C., Tan, S. H., & Barker, N. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.01.010 · Cited by 157 · see citing works
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration
Aloia, L., McKie, M. A., Vernaz, G., Cordero-Espinoza, L., Aleksieva, N., van den Ameele, J., Antonica, F., Font-Cunill, B., Raven, A., Aiese Cigliano, R., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0402-6 · Cited by 160 · see citing works
Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells
Castelli, G., Pelosi, E., & Testa, U. (2017) · Cancers · doi:10.3390/cancers9090127 · Cited by 157 · see citing works
Multi-organ Mapping of Cancer Risk
Zhu, L., Finkelstein, D., Gao, C., Shi, L. G., Wang, Y., Lopez-Terrada, D. H., Wang, K. S., Utley, S., Pounds, S. B., Neale, G. A. M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.07.045 · Cited by 154 · see citing works
Radiation‐induced tissue damage and response
McBride, W. H., & Schaue, D. (2020) · The Journal of Pathology · doi:10.1002/path.5389 · Cited by 155 · see citing works
Adebayo Michael, A. O., Ko, S., Tao, J., Moghe, A., Yang, H., Xu, M., Russell, J. O., Pradhan-Sundd, T., Liu, S., Singh, S., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.002 · Cited by 155 · see citing works
Duan, J., Ruan, B., Yan, X., Liang, L., Song, P., Yang, Z., Liu, Y., Dou, K., Han, H., & Wang, L. (2018) · Hepatology · doi:10.1002/hep.29834 · Cited by 153 · see citing works
AQP5 enriches for stem cells and cancer origins in the distal stomach
Tan, S. H., Yada, S., Tan, S., Goh, J., Seishima, R., Murakami, K., Oshima, M., Tsuji, T., Phuah, P., Tan, L. T., et al. (2020) · Nature · doi:10.1038/s41586-020-1973-x · Cited by 153 · see citing works
Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo
Miao, Y., Ha, A., de Lau, W., Yuki, K., Santos, A. J. M., You, C., Geurts, M. H., Puschhof, J., Pleguezuelos-Manzano, C., Peng, W. C., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.07.020 · Cited by 151 · see citing works
Self-citationCellular plasticity in kidney injury and repair
Chang-Panesso, M., & Humphreys, B. D. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.169 · Cited by 149 · see citing works
The Endothelium as a Driver of Liver Fibrosis and Regeneration
Lafoz, E., Ruart, M., Anton, A., Oncins, A., & Hernández–Gea, V. (2020) · Cells · doi:10.3390/cells9040929 · Cited by 147 · see citing works
Gli1+ Periodontium Stem Cells Are Regulated by Osteocytes and Occlusal Force
Men, Y., Wang, Y., Yi, Y., Jing, D., Luo, W., Shen, B., Stenberg, W. V., Chai, Y., Ge, W., Feng, J. Q., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.006 · Cited by 149 · see citing works
Space-time logic of liver gene expression at sub-lobular scale
Droin, C., Kholtei, J. E., Bahar Halpern, K., Hurni, C., Rozenberg, M., Muvkadi, S., Itzkovitz, S., & Naef, F. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00323-1 · Cited by 148 · see citing works
Wnt/β-catenin signaling in adult mammalian epithelial stem cells
Kretzschmar, K., & Clevers, H. C. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.05.015 · Cited by 144 · see citing works
Pathogenesis of Cholangiocarcinoma
Rodrigues, P. M., Olaizola, P., Paiva, N. A., Olaizola, I., Lizaso, A. A., Landa-Magdalena, A., Bujanda, L., Perugorria, M. J., & Bañales, J. M. (2020) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-030220-020455 · Cited by 143 · see citing works
Acquisition of epithelial plasticity in human chronic liver disease
Gribben, C., Galanakis, V., Calderwood, A., Williams, E. C., Chazarra-Gil, R., Larraz, M., Frau, C., Puengel, T., Guillot, A., Rouhani, F. J., et al. (2024) · Nature · doi:10.1038/s41586-024-07465-2 · Cited by 142 · see citing works
Epithelial Plasticity during Liver Injury and Regeneration
Gadd, V. L., Aleksieva, N., & Forbes, S. J. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.08.016 · Cited by 142 · see citing works
Multimodal decoding of human liver regeneration
Matchett, K. P., Wilson-Kanamori, J. R., Portman, J. R., Kapourani, C. A., Fercoq, F., May, S., Zajdel, E., Beltran, M., Sutherland, E. F., Mackey, J. B. G., et al. (2024) · Nature · doi:10.1038/s41586-024-07376-2 · Cited by 140 · see citing works
Modeling Human Digestive Diseases With CRISPR-Cas9–Modified Organoids
Fujii, M., Clevers, H. C., & Sato, T. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.11.048 · Cited by 140 · see citing works
A critical perspective on 3D liver models for drug metabolism and toxicology studies
Serras, A. S., Rodrigues, J. S., Cipriano, M., Rodrigues, A. V., Oliveira, N. G., & Miranda, J. P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.626805 · Cited by 138 · see citing works
Mfsd2a+ hepatocytes repopulate the liver during injury and regeneration
Pu, W., Zhang, H., Huang, X., Tian, X., He, L., Wang, Y., Zhang, L., Liu, Q., Li, Y., Li, Y., et al. (2016) · Nature Communications · doi:10.1038/ncomms13369 · Cited by 136 · see citing works
Preziosi, M., Okabe, H., Poddar, M., Singh, S., & Monga, S. P. (2018) · Hepatology Communications · doi:10.1002/hep4.1196 · Cited by 135 · see citing works
Désert, R., Rohart, F., Canal, F., Sicard, M., Desille, M., Renaud, S., Turlin, B., Bellaud, P., Perret, C., Clément, B., et al. (2017) · Hepatology · doi:10.1002/hep.29254 · Cited by 134 · see citing works
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics
Ma, X., Huang, T., Chen, X., Li, Q., Liao, M., Fu, L., Huang, J., Yuan, K., Wang, Z., & Zeng, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02104-8 · Cited by 133 · see citing works
The roles of Wnt/β‐catenin pathway in tissue development and regenerative medicine
Majidinia, M., Javad, A., Jahanban‐Esfahlan, R., & Yousefi, B. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26265 · Cited by 133 · see citing works
Understanding the marvels behind liver regeneration
Rmilah, A. A. A., Zhou, W., Nelson, E., Li, L., Amiot, B. P., & Nyberg, S. L. (2019) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.340 · Cited by 133 · see citing works
Gieseck, R. L., Ramalingam, T. R., Hart, K. M., Vannella, K. M., Cantu, D. A., Lu, W.-Y., Ferreira-González, S., Forbes, S. J., Vallier, L., & Wynn, T. A. (2016) · Immunity · doi:10.1016/j.immuni.2016.06.009 · Cited by 132 · see citing works
- Authors
- Wang, B., Zhao, L., Fish, M., Logan, C. Y., & Nusse, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wang, Bruce
- Venue
- Nature
- Published
- 2015-08-05
- Volume
- 524
- Issue
- 7564
- Pages
- 180-185
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4589224
- OpenAlex
- W1628437161
- Cited by
- 674
- References
- 50
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 33 · 2023: 61 · 2022: 52 · 2021: 90 · 2020: 88 · 2019: 66 · 2018: 85 · 2017: 69 · 2016: 67 · 2015: 19
- FWCI
- 47.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK101603, F32DK091005, P30DK026743)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- liver homeostasis, Axin2, Wnt signaling, TBX3, liver progenitor cells, polyploidy, self-renewal, stem cell niche, lineage tracing
- MeSH terms
- Animals, Clone Cells, Diploidy, Female, Homeostasis, Liver, Male, Polyploidy, Regeneration, Staining and Labeling, Stem Cells, Time Factors, Veins, Biomarkers, Cell Lineage, T-Box Domain Proteins, Hepatocytes, Endothelial Cells, Cell Proliferation, Mice, Stem Cell Niche, Wnt Signaling Pathway, Axin Protein
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