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HomeNatureMacrophages harness hepatocyte glutamate to boost liver regeneration

Macrophages harness hepatocyte glutamate to boost liver regeneration

  • Rigual, M. D. M., Sanchez Sanchez, P. & Djouder, N. Is liver regeneration key in hepatocellular carcinoma development? Trends Cancer 9, 140–157 (2023).

    PubMed 

    Google Scholar
     

  • Martini, T., Naef, F. & Tchorz, J. S. Spatiotemporal metabolic liver zonation and consequences on pathophysiology. Annu. Rev. Pathol. 18, 439–466 (2023).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Gordillo, M., Evans, T. & Gouon-Evans, V. Orchestrating liver development. Development 142, 2094–2108 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, B. et al. Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver. Nature 524, 180–185 (2015).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Sun, T. et al. AXIN2+ pericentral hepatocytes have limited contributions to liver homeostasis and regeneration. Cell Stem Cell 26, 97–107 (2020).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • May, S. et al. Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration. J. Hepatol. 78, 1028–1036 (2023).

    CAS 
    PubMed 

    Google Scholar
     

  • Chen, F. et al. Broad distribution of hepatocyte proliferation in liver homeostasis and regeneration. Cell Stem Cell 26, 27–33 (2020).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Matsumoto, T. et al. In vivo lineage tracing of polyploid hepatocytes reveals extensive proliferation during liver regeneration. Cell Stem Cell 26, 34–47 (2020).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Wei, Y. et al. Liver homeostasis is maintained by midlobular zone 2 hepatocytes. Science 371, eabb1625 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • He, L. et al. Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair. Science 371, eabc4346 (2021).

    CAS 
    PubMed 

    Google Scholar
     

  • Ben-Moshe, S. et al. Spatial sorting enables comprehensive characterization of liver zonation. Nat. Metab. 1, 899–911 (2019).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Herranz-Montoya, I., Park, S. & Djouder, N. A comprehensive analysis of prefoldins and their implication in cancer. iScience 24, 103273 (2021).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Tummala, K. S. et al. Inhibition of de novo NAD+ synthesis by oncogenic URI causes liver tumorigenesis through DNA damage. Cancer Cell 26, 826–839 (2014).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Xu, J. et al. A spatiotemporal atlas of mouse liver homeostasis and regeneration. Nat. Genet. 56, 953–969 (2024).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • MacParland, S. A. et al. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat. Commun. 9, 4383 (2018).

    ADS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Chaves-Perez, A. et al. URI is required to maintain intestinal architecture during ionizing radiation. Science 364, eaaq1165 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • Schuler, M. et al. Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse. Genesis 39, 167–172 (2004).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Nivison-Smith, L. et al. Retinal amino acid neurochemistry of the southern hemisphere lamprey, Geotria australis. PLoS ONE 8, e58406 (2013).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mitchell, C. & Willenbring, H. A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat. Protoc. 3, 1167–1170 (2008).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • He, Y. et al. Glutamine synthetase deficiency in murine astrocytes results in neonatal death. Glia 58, 741–754 (2010).

    PubMed 
    MATH 

    Google Scholar
     

  • Bellisle, F. et al. Monosodium glutamate as a palatability enhancer in the European diet. Physiol. Behav. 49, 869–873 (1991).

    CAS 
    PubMed 

    Google Scholar
     

  • Celestino, M. et al. Differential effects of sodium chloride and monosodium glutamate on kidney of adult and aging mice. Sci. Rep. 11, 481 (2021).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Heymann, F. & Tacke, F. Immunology in the liver–from homeostasis to disease. Nat. Rev. Gastroenterol. Hepatol. 13, 88–110 (2016).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Gras, G. et al. EAAT expression by macrophages and microglia: still more questions than answers. Amino Acids 42, 221–229 (2012).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Krenkel, O. & Tacke, F. Liver macrophages in tissue homeostasis and disease. Nat. Rev. Immunol. 17, 306–321 (2017).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Lachmann, A. et al. ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26, 2438–2444 (2010).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Selak, M. A. et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7, 77–85 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Koivunen, P. et al. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J. Biol. Chem. 282, 4524–4532 (2007).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Hewitson, K. S. et al. Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates. J. Biol. Chem. 282, 3293–3301 (2007).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Ryan, H. E. et al. Hypoxia-inducible factor-1α is a positive factor in solid tumor growth. Cancer Res. 60, 4010–4015 (2000).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Clausen, B. E. et al. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 8, 265–277 (1999).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Annunziato, S., Sun, T. & Tchorz, J. S. The RSPO-LGR4/5-ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease. Hepatology 76, 888–899 (2022).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Boulter, L. et al. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat. Med. 18, 572–579 (2012).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • CZI Cell Science Program et al. CZ CELLxGENE Discover: a single-cell data platform for scalable exploration, analysis and modeling of aggregated data. Nucleic Acids Res. https://doi.org/10.1093/nar/gkae1142 (2023).

  • Grant, C. E., Bailey, T. L. & Noble, W. S. FIMO: scanning for occurrences of a given motif. Bioinformatics 27, 1017–1018 (2011).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Azzolin, L. et al. YAP/TAZ incorporation in the beta-catenin destruction complex orchestrates the Wnt response. Cell 158, 157–170 (2014).

    CAS 
    PubMed 

    Google Scholar
     

  • Robanus-Maandag, E. C. et al. A new conditional Apc-mutant mouse model for colorectal cancer. Carcinogenesis 31, 946–952 (2010).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Brault, V. et al. Inactivation of the β-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128, 1253–1264 (2001).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Zhang, N. et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev. Cell 19, 27–38 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, Y. & Danbolt, N. C. Glutamate as a neurotransmitter in the healthy brain. J. Neural Transm. 121, 799–817 (2014).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Nair, A. B. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27–31 (2016).

    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Qvartskhava, N. et al. Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase. Proc. Natl Acad. Sci. USA 112, 5521–5526 (2015).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Garrido, A. et al. Histone acetylation of bile acid transporter genes plays a critical role in cirrhosis. J. Hepatol. https://doi.org/10.1016/j.jhep.2021.12.019 (2021).

  • Lau, A. & Tymianski, M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch. 460, 525–542 (2010).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Bhushan, B. et al. TCPOBOP-induced hepatomegaly and hepatocyte proliferation are attenuated by combined disruption of MET and EGFR signaling. Hepatology 69, 1702–1718 (2019).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Fukuchi, T. et al. Effects of portal-systemic shunt following 90% partial hepatectomy in rats. J. Surg. Res. 89, 126–131 (2000).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Myronovych, A. et al. Role of platelets on liver regeneration after 90% hepatectomy in mice. J. Hepatol. 49, 363–372 (2008).

    CAS 
    PubMed 

    Google Scholar
     

  • Ramachandran, P. et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575, 512–518 (2019).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Ma, L. et al. Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell 36, 418–430 (2019).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Tummala, K. S. et al. Hepatocellular carcinomas originate predominantly from hepatocytes and benign lesions from hepatic progenitor cells. Cell Rep. 19, 584–600 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gomes, A. L. et al. Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma. Cancer Cell 30, 161–175 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • Cramer, T. et al. HIF-1α is essential for myeloid cell-mediated inflammation. Cell 112, 645–657 (2003).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Li, W. et al. Monocyte-derived Kupffer cells dominate in the Kupffer cell pool during liver injury. Cell Rep. 42, 113164 (2023).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Shi, C. & Pamer, E. G. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 11, 762–774 (2011).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Zwicker, C., Bujko, A. & Scott, C. L. Hepatic macrophage responses in inflammation, a function of plasticity, heterogeneity or both? Front. Immunol. 12, 690813 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kistner, A. et al. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc. Natl Acad. Sci. USA 93, 10933–10938 (1996).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Fawal, M. A., Brandt, M. & Djouder, N. MCRS1 binds and couples rheb to amino acid-dependent mTORC1 activation. Dev. Cell 33, 67–82 (2015).

    CAS 
    PubMed 

    Google Scholar
     

  • Dupre, A. et al. Associating portal embolization and artery ligation to induce rapid liver regeneration in staged hepatectomy. Br. J. Surg. 102, 1541–1550 (2015).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Okabe, H. et al. Percentage of future liver remnant volume before portal vein embolization influences the degree of liver regeneration after hepatectomy. J. Gastrointest. Surg. 17, 1447–1451 (2013).

    PubMed 
    MATH 

    Google Scholar
     

  • Teijeiro, A. et al. Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice. Nat. Metab. 3, 496–512 (2021).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Buren, S. et al. Regulation of OGT by URI in response to glucose confers c-MYC-dependent survival mechanisms. Cancer Cell 30, 290–307 (2016).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Djouder, N. et al. S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Mol. Cell 28, 28–40 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • Bueno Batista, M. et al. Disrupting hierarchical control of nitrogen fixation enables carbon-dependent regulation of ammonia excretion in soil diazotrophs. PLoS Genet. 17, e1009617 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Andreatta, M. & Carmona, S. J. UCell: robust and scalable single-cell gene signature scoring. Comput. Struct. Biotechnol. J. 19, 3796–3798 (2021).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Zhang, P. et al. Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance. Genome Biol. 23, 136 (2022).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

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