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Liver homeostasis is maintained by midlobular zone 2 hepatocytes
Open accessAbstract
Zoning in on liver growth: For organ homeostasis or regrowth after injury or disease, one or more stem cell populations is needed to rebuild lost tissue. There is considerable debate about the source of new cells in the liver. Two groups now identify the source of new hepatocytes (see the Perspective by Andersson). Although the liver may seem to lack major variation across its structure, its lobule is organized into concentric zones where hepatocytes express different metabolic enzymes. Wei et al. sought to systematically define the source of new liver cells by comparing 14 fate-mapping mice that label different liver cell types. They found that different regions of the liver lobule exhibit differences in hepatocyte turnover, with zone 2 representing a primary source of new hepatocytes during homeostasis and regeneration. Similarly, He et al. designed a genetic approach to record cell proliferation in vivo with high spatial and temporal resolution to enable continuous recording of proliferative events of any specific cell type at the whole-cell population level. Using this method, they identified zone 2 as having the highest proliferative activity and contributing the most to liver regrowth. These findings have implications for the cellular basis of chronic disease pathogenesis, cancer development, and regenerative medicine strategies. Science , this issue p. eabb1625 , p. eabc4346 ; see also p. 887
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“To annotate clusters by zone and cell type, known marker genes were used (18), including markers for hepatic zones (zone-specific genes), bile duct cells, Kupffer cells, endothelial cells, hepatic stellate cells, and lymphocytes.”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [18]
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“Instead, EdU incorporation suggested that knocking CreERT2 into the endogenous Axin2 locus increases proliferation of hepatocytes due to heterozygous Axin2 deletion.86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“Additionally, sparsely labelled hepatocytes, marked by novel Cre-expressing transgenes from the Hamp2 and Mup3 promoters, also expanded during homeostasis, demonstrating that proliferation is not limited to the high telomerase-expressing population.86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“Additionally, injury to zone 1 by allyl alcohol injection or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet was compensated by proliferation of hepatocytes in zones 2 and 3.85,86,88”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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In the citing paper
“Zone 2 hepatocytes labelled by AAV8-TBG-Cre or CreERT2 expressed from the Hamp2 or Mup3 promoters also proliferated and clonally expanded.86,88”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“Additionally, hepatocytes traced from the Hamp2 and Mup3 promoters readily gave rise to hepatocyte clusters after CCl4 and DDC injury.86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“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 [18]
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“Analysis using qPCR and IHC suggested that this effect was mediated by RSPO3-dependent regulation of the WNT target CCND1 (Fig. 4a and Extended Data Figs. 7a and 10b), a key driver of liver regeneration23,42.”
From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [42]
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“Corresponding to the predominantly midzonal alterations in WNT-target genes as a result of a condensed zone 3 and an expanded zone 1 (Fig. 3i and Extended Data Fig. 8c), the alterations in proliferation and liver injury in Rspo3ΔHSC mice were most pronounced in the hepatic midzone (Fig. 4e and Extended Data Fig. 10b), which is pivotal for hepatocyte regeneration42.”
From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [42]
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“The recent generation of mice with Cre recombinase activity in distinct zonal populations permitted us to induce HCC mutations in a variety of normal cell types (18).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [18]
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“Cyp1a2-CreER mice recombine loci in zones 2 and 3, but more frequently in zone 3 (18).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [18]
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“During homeostasis, zone 2 hepatocytes rather than a defined subpopulation seem to have increased proliferative potential.”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“Nevertheless, hepatocytes do not proliferate equally over time, as results obtained via three independent experimental approaches have led to the same conclusion, namely that zone 2 hepatocytes proliferate more than hepatocytes from the other zones.75,86,88”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“Hepatocyte proliferation in zone 2 hepatocytes is mediated by the IGFBP2-mTOR-CCND1 axis.86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“A comprehensive study using several new mouse transgenic lines to label different portions of the lobule also demonstrated that zone 2 hepatocytes expand during homeostasis, with a corresponding contraction of the areas originally occupied by zone 1 or 3 hepatocytes.86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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“Alternative zone 3 labelling with other gene promoters also did not show that zone 3 hepatocytes give rise to hepatocytes in other zones during homeostasis.44,50,86”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [86]
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Cites
Fast unfolding of communities in large networks
Blondel, V. D., Guillaume, J.-L., Lambiotte, R., & Lefebvre, E. (2008) · Journal of Statistical Mechanics: Theory and Experiment · doi:10.1088/1742-5468/2008/10/p10008 · Cited by 21,424
SCANPY: large-scale single-cell gene expression data analysis
Wolf, F. A., Angerer, P., & Theis, F. J. (2018) · Genome Biology · doi:10.1186/s13059-017-1382-0 · Cited by 8,881
From Louvain to Leiden: guaranteeing well-connected communities
Traag, V. A., Waltman, L., & van Eck, N. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-41695-z · Cited by 5,635
Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors
Haghverdi, L., Lun, A. T. L., Morgan, M. D., & Marioni, J. C. (2018) · Nature Biotechnology · doi:10.1038/nbt.4091 · Cited by 2,416
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Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations
MacParland, S. A., Liu, J. C., Ma, X.-Z., Innes, B. T., Bartczak, A. M., Gage, B. K., Manuel, J., Khuu, N., Echeverri, J., Linares, I., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06318-7 · Cited by 1,552
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
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
Furuyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2010) · Nature Genetics · doi:10.1038/ng.722 · Cited by 841
Sadana, P., Geyer, R., Pezoldt, J., Helmsing, S., Huehn, J., Hust, M., Dersch, P., & Scrima, A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.001068 · Cited by 721
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Hu, S., Liu, S., Bian, Y., Poddar, M., Singh, S., Cao, C., McGaughey, J., Bell, A., Blazer, L. L., Adams, J. J., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100754 · Cited by 118
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Li, Z., Pai, R., Gupta, S., Currenti, J., Guo, W., Bartolomeo, A. D., Feng, H., Zhang, Z., Li, Z., Liu, L., et al. (2024) · Nature Cancer · doi:10.1038/s43018-023-00672-2 · Cited by 107
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Fu, X., He, Q., Tao, Y., Wang, M., Wang, W., Wang, Y., Yu, Q. C., Zhang, F., Zhang, X., Chen, Y., et al. (2021) · Science China Life Sciences · doi:10.1007/s11427-021-2007-8 · Cited by 30
Self-citationOderberg, I. M., & Goessling, W. (2023) · JCI Insight · doi:10.1172/jci.insight.163929 · Cited by 30
Seubnooch, P., Montani, M., Tsouka, S., Claude, E., Rafiqi, U., Perren, A. A., Dufour, J., & Masoodi, M. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100725 · Cited by 30
Direct mechanical exposure initiates hepatocyte proliferation
Li, W., Wu, Y. C., Hu, W., Zhou, J., Shu, X., Zhang, X., Zhang, Z., Wu, H. C., Du, Y. M., Lü, D., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100905 · Cited by 28
Feng, D., Guan, Y., Wang, Y., Maccioni, L., Mackowiak, B., & Gao, B. (2025) · eGastroenterology · doi:10.1136/egastro-2025-100189 · Cited by 29
Self-citationHarnessing orthogonal recombinases to decipher cell fate with enhanced precision
Weng, W., Liu, X., Lui, K. O., & Zhou, B. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.09.007 · Cited by 26
Hepatocyte generation in liver homeostasis, repair, and regeneration
Pu, W., & Zhou, B. (2022) · Cell Regeneration · doi:10.1186/s13619-021-00101-8 · Cited by 25
State-of-the-art advancements in Liver-on-a-chip (LOC): Integrated biosensors for LOC
Liu, M., Xiang, Y., Yang, Y., Long, X., Xiao, Z., Nan, Y., Jiang, Y., Qiu, Y., Huang, Q., & Ai, K. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2022.114758 · Cited by 28
Is liver regeneration key in hepatocellular carcinoma development?
Rigual, M. D. M., Sánchez, P. S., & Djouder, N. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.10.005 · Cited by 28
Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver
Tramunt, B., Montagner, A., Tan, N. S., Gourdy, P., Rémignon, H., & Wahli, W. (2021) · Metabolites · doi:10.3390/metabo11080502 · Cited by 27
Novel Insights Into the Mechanism of GVHD-Induced Tissue Damage
Ara, T., & Hashimoto, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.713631 · Cited by 26
Cell transplantation-based regenerative medicine in liver diseases
Cardinale, V., Lanthier, N., Baptista, P. M., Carpino, G., Carnevale, G., Orlando, G., Angelico, R., Manzia, T. M., Schuppan, D., Pinzani, M., et al. (2023) · Stem Cell Reports · doi:10.1016/j.stemcr.2023.06.005 · Cited by 27
Ruz‐Maldonado, I., González, J. T., Zhang, H., Sun, J., Bort, A., Kabir, I., Kibbey, R. G., Suárez, Y., Greif, D. M., & Fernandez-Hernando, C. F. (2024) · Nature Communications · doi:10.1038/s41467-024-45439-0 · Cited by 26
The origin of hepatocellular carcinoma depends on metabolic zonation
Guo, J., Liang, R., Chung, A., Li, Z., Li, B., Chen, E., Li, L., Wang, J., Hsieh, M.-H., Fang, I. X., et al. (2026) · Science · doi:10.1126/science.adv7129 · Cited by 24
Self-citationSpatial regulation of glucose and lipid metabolism by hepatic insulin signaling
He, B., Copps, K. D., Stöhr, O., Liu, B., Hu, S., Joshi, S., Haigis, M. C., White, M. F., Zhu, H., & Tao, R. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.03.015 · Cited by 30
Self-citationNovel insights into liver homeostasis and regeneration
Michalopoulos, G. K. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00454-0 · Cited by 25
Sarkar, A., Jin, Y., DeFelice, B. C., Logan, C. Y., Yang, Y., Anbarchian, T., Wu, P. V., Morri, M., Neff, N. F., Nguyen, H., et al. (2022) · eLife · doi:10.7554/elife.82311 · Cited by 23
Lipid droplet deposition in the regenerating liver: A promoter, inhibitor, or bystander?
Hu, Y., Wang, R., Liu, J., Wang, Y., & Dong, J. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000267 · Cited by 22
Self-citationIn the zone for liver proliferation
Andersson, E. R. (2021) · Science · doi:10.1126/science.abg4864 · Cited by 23
Nagai, H., Nagai, L. A. E., Tasaki, S., Nakato, R., Umetsu, D., Kuranaga, E., Miura, M., & Nakajima, Y.-I. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.08.022 · Cited by 23
Kakazu, E., Mino, M., & Kanto, T. (2025) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2025.0048 · Cited by 24
Decoding liver fibrogenesis with single-cell technologies
Zhou, T., Musunuru, K., Lui, K. O., & Ding, Q. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac040 · Cited by 22
Hepatocyte reprogramming in liver regeneration: Biological mechanisms and applications
Jiang, M., Ren, J., Belmonte, J. C. I., & Liu, G. (2023) · FEBS Journal · doi:10.1111/febs.16930 · Cited by 20
FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes
Liang, C.-Q., Zhou, D., Peng, W., Chen, W.-Y., Wu, H., Zhou, Y.-M., Gu, W., Park, K., Zhao, H., Pi, L., et al. (2022) · npj Regenerative Medicine · doi:10.1038/s41536-022-00227-6 · Cited by 18
Highly stable bismuth-chloride perovskite X-ray direct detectors with an ultralow detection limit
Chen, H., Han, Q., Qin, H., Shen, Y., Lv, H., Liu, Y., Du, L., Wang, Y., He, Y., & Ning, W. (2025) · Chemical Science · doi:10.1039/d5sc00061k · Cited by 19
Self-citationCabanes‐Creus, M., Navarro, R. G., Liao, S. H. Y., Scott, S., Carlessi, R., Roca-Pinilla, R., Knight, M., Baltazar, G., Zhu, E., Jones, M., et al. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.12.014 · Cited by 20
Li, S., Li, C., Khan, M. I., Liu, J., Shi, Z., Gao, D. Y., Qiu, B., & Ding, W. (2023) · Microsystems & Nanoengineering · doi:10.1038/s41378-023-00544-w · Cited by 20
Zonation, Zonation, Zonation: The Real Estate of the Liver
Yasaka, T. M., Kim, C., Meadows, V., & Monga, S. P. (2025) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-042624-091820 · Cited by 28
Akiyama, S., Saku, N., Miyata, S., Ite, K., Toyoda, M., Kimura, T., Kuroda, M., Nakazawa, A., Kasahara, M., Nonaka, H., et al. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02776-5 · Cited by 17
Zhang, S., Zatulovskiy, E. A., Arand, J., Sage, J., & Skotheim, J. M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.965595 · Cited by 21
Self-citationMultiple Facets of Cellular Homeostasis and Regeneration of the Mammalian Liver
Huppert, S. S., & Schwartz, R. E. (2022) · Annual Review of Physiology · doi:10.1146/annurev-physiol-032822-094134 · Cited by 21
A statistical method for quantifying progenitor cells reveals incipient cell fate commitments
Deng, S., Gong, H., Zhang, D., Zhang, M., & He, X. (2024) · Nature Methods · doi:10.1038/s41592-024-02189-7 · Cited by 19
ScRNA-seq and ST-seq in liver research
He, J., Deng, C., Krall, L., & Shan, Z. (2023) · Cell Regeneration · doi:10.1186/s13619-022-00152-5 · Cited by 18
Okada, J., Landgraf, A., Xiaoli, A. M., Liu, L. P., Horton, M., Schuster, V. L., Yang, F., Sidoli, S., Qiu, Y., Kurland, I. J., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01269-y · Cited by 19
Iwasawa, K., & Takebe, T. (2021) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2021.06.007 · Cited by 19
Compartmentalization, cooperation, and communication: The 3Cs of Hepatocyte zonation
Porat‐Shliom, N. (2023) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2023.102292 · Cited by 16
Relationships Between Regeneration, Wound Healing, and Cancer
Maggiore, G., & Zhu, H. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062822-123558 · Cited by 18
Self-citationPlata-Gómez, A. B., de Prado-Rivas, L., Sanz, A., Deleyto-Seldas, N., García, F., de la Calle Arregui, C., Silva, C., Caleiras, E., Graña-Castro, O., Piñeiro-Yáñez, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46032-1 · Cited by 16
Tissue regeneration: Unraveling strategies for resolving pathological fibrosis
Li, J., Wang, S., Yuan, J., Mao, X., Wang, X., Zhang, L., Dong, Q., Chen, Z., Wang, Y., & Tang, N. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.10.002 · Cited by 19
Self-citationEmerging and potential use of CRISPR in human liver disease
Adlat, S., Vázquez-Salgado, A. M., Lee, M., Yin, D., & Wangensteen, K. J. (2023) · Hepatology · doi:10.1097/hep.0000000000000578 · Cited by 19
Spatial-temporal proliferation of hepatocytes during pregnancy revealed by genetic lineage tracing
He, S., Guo, Z., Zhou, M., Wang, H., Zhang, Z., Shi, M., Li, X., Yang, X., & He, L. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.09.002 · Cited by 17
Yi, B., Pan, J., Yang, Z., Zhu, Z., Sun, Y., Guo, T., & Zhao, Z. (2024) · Molecular and Cellular Probes · doi:10.1016/j.mcp.2024.101958 · Cited by 15
Metadata
- Authors
- Wei, Y., Wang, Y. G., Jia, Y., Li, L., Yoon, J., Zhang, S., Wang, Z., Zhang, Y., Zhu, M., Sharma, T., Lin, Y.-H., Hsieh, M.-H., Albrecht, J. H., Le, P. T., Rosen, C. J., Wang, T., & Zhu, H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Minnesota (US)
- Maine Medical Center (US)
- Corresponding author
- Zhu, Hao
- ORCID
- Venue
- Science
- Published
- 2021-02-26
- Volume
- 371
- Issue
- 6532
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8496420
- OpenAlex
- W3132549301
- Cited by
- 292
- References
- 43
- Citations by year
- 2026: 37 · 2025: 60 · 2024: 39 · 2023: 73 · 2022: 53 · 2021: 30
- FWCI
- 27.13
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01 CA251928)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK111588)
- National Institute of Environmental Health Sciences (R03ES026397-01)
- Burroughs Wellcome Fund
- Cancer Prevention and Research Institute of Texas (RP150596, RP190208)
- Stand Up To Cancer (SU2C-AACR-IRG 10-16)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- liver homeostasis, hepatocyte proliferation, liver regeneration, hepatocyte turnover, fate mapping, cell proliferation imaging, liver stem cells
- MeSH terms
- Animals, Biliary Tract, Biliary Tract Diseases, Homeostasis, Liver, Liver Regeneration, Insulin-Like Growth Factor Binding Protein 2, Cyclin D1, Hepatocytes, Cell Proliferation, Mice, Gene Knock-In Techniques, TOR Serine-Threonine Kinases
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