{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:38:25Z","timestamp":1791596305702,"version":"4.3.4"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T00:00:00Z","timestamp":1676678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T00:00:00Z","timestamp":1676678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270898"],"award-info":[{"award-number":["82270898"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973418"],"award-info":[{"award-number":["81973418"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7212148"],"award-info":[{"award-number":["7212148"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002888","name":"Beijing Municipal Commission of Education","doi-asserted-by":"publisher","award":["KM202110025023"],"award-info":[{"award-number":["KM202110025023"]}],"id":[{"id":"10.13039\/501100002888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hepatic ischemia-reperfusion (I\/R) injury is a common complication in liver transplantation. The connection between I\/R-induced injury response and liver heterogeneity has yet to be fully understood. In this study, we converge histopathological examination with spatial transcriptomics to dissect I\/R injury patterns and their associated molecular changes, which reveal that the pericentral zones are most sensitive to I\/R injury in terms of histology, transcriptomic changes, and cell type dynamics. Bioinformatic analysis of I\/R injury-related pathways predicts that celastrol can protect against liver I\/R injury by inducing ischemic pre-conditioning, which is experimentally validated. Mechanistically, celastrol likely implements its protective effect against I\/R injury by activating HIF1\u03b1 signaling and represents a potential strategy for resolving liver I\/R.<\/jats:p>","DOI":"10.1038\/s42003-023-04564-0","type":"journal-article","created":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T04:47:39Z","timestamp":1676695659000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Spatial transcriptomics analysis of zone-dependent hepatic ischemia-reperfusion injury murine model"],"prefix":"10.1038","volume":"6","author":[{"given":"Jiaqi","family":"Xin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4446-984X","authenticated-orcid":false,"given":"Mengxi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3081-9642","authenticated-orcid":false,"given":"Wei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,18]]},"reference":[{"key":"4564_CR1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jhep.2019.05.029","volume":"71","author":"Y Liu","year":"2019","unstructured":"Liu, Y. et al. Activation of YAP attenuates hepatic damage and fibrosis in liver ischemia-reperfusion injury. J. Hepatol. 71, 719\u2013730 (2019).","journal-title":"J. Hepatol."},{"key":"4564_CR2","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1097\/01.sla.0000098620.27623.7d","volume":"238","author":"PA Clavien","year":"2003","unstructured":"Clavien, P. A. et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann. Surg. 238, 843\u2013850 (2003).","journal-title":"Ann. Surg."},{"key":"4564_CR3","volume":"10","author":"K Arnold","year":"2020","unstructured":"Arnold, K. et al. Synthetic anticoagulant heparan sulfate attenuates liver ischemia reperfusion injury. Sci. Rep. 10, 17187 (2020).","journal-title":"Sci. Rep."},{"key":"4564_CR4","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature21065","volume":"542","author":"KB Halpern","year":"2017","unstructured":"Halpern, K. B. et al. Single-cell spatial reconstruction reveals global division of labour in the mammalian liver. Nature 542, 352\u2013356 (2017).","journal-title":"Nature"},{"key":"4564_CR5","unstructured":"No\u00ebl, R. Recherches histo-physiologiques sur la cellule h\u00e9patique des mammif\u00e8res (Univ. de Paris, 1922)."},{"key":"4564_CR6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/ar.1090880104","volume":"88","author":"HW Deane","year":"1944","unstructured":"Deane, H. W. A cytological study of the diurnal cycle of the liver of the mouse in relation to storage and secretion. Anat. Rec. 88, 39\u201365 (1944).","journal-title":"Anat. Rec."},{"key":"4564_CR7","doi-asserted-by":"crossref","first-page":"eabb1625","DOI":"10.1126\/science.abb1625","volume":"371","author":"Y Wei","year":"2021","unstructured":"Wei, Y. et al. Liver homeostasis is maintained by midlobular zone 2 hepatocytes. Science 371, eabb1625 (2021).","journal-title":"Science"},{"key":"4564_CR8","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/0006-2952(93)90277-4","volume":"45","author":"I Anundi","year":"1993","unstructured":"Anundi, I., L\u00e4hteenm\u00e4ki, T., Rundgren, M., Moldeus, P. & Lindros, K. O. Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes. Biochem Pharm. 45, 1251\u20131259 (1993).","journal-title":"Biochem Pharm."},{"key":"4564_CR9","first-page":"695","volume":"34","author":"PE Ganey","year":"1988","unstructured":"Ganey, P. E., Kauffman, F. C. & Thurman, R. G. Oxygen-dependent hepatotoxicity due to doxorubicin: role of reducing equivalent supply in perfused rat liver. Mol. Pharmacol. 34, 695 (1988).","journal-title":"Mol. Pharmacol."},{"key":"4564_CR10","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/s42255-019-0109-9","volume":"1","author":"S Ben-Moshe","year":"2019","unstructured":"Ben-Moshe, S. et al. Spatial sorting enables comprehensive characterization of liver zonation. Nat. Metab. 1, 899\u2013911 (2019).","journal-title":"Nat. Metab."},{"key":"4564_CR11","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1016\/j.celrep.2019.10.024","volume":"29","author":"R Dobie","year":"2019","unstructured":"Dobie, R. et al. Single-cell transcriptomics uncovers zonation of function in the mesenchyme during liver fibrosis. Cell Rep. 29, 1832\u20131847.e8 (2019).","journal-title":"Cell Rep."},{"key":"4564_CR12","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/toxsci\/kfab052","volume":"182","author":"DS Umbaugh","year":"2021","unstructured":"Umbaugh, D. S., Ramachandran, A. & Jaeschke, H. Spatial reconstruction of the early hepatic transcriptomic landscape after an acetaminophen overdose using single-cell RNA-sequencing. Toxicol. Sci. 182, 327\u2013345 (2021).","journal-title":"Toxicol. Sci."},{"key":"4564_CR13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.26574\/maedica.2018.13.1.5","volume":"13","author":"AO Ciobanu","year":"2018","unstructured":"Ciobanu, A. O. & Gherasim, L. Ischemic hepatitis\u2013intercorrelated pathology. Maedica 13, 5\u201311 (2018).","journal-title":"Maedica"},{"key":"4564_CR14","doi-asserted-by":"crossref","first-page":"e922306","DOI":"10.12659\/AOT.922306","volume":"25","author":"S Nakanuma","year":"2020","unstructured":"Nakanuma, S. et al. Pretreatment with a phosphodiesterase-3 inhibitor, milrinone, reduces hepatic ischemia-reperfusion injury, minimizing pericentral zone-based liver and small intestinal injury in rats. Ann. Transpl. 25, e922306 (2020).","journal-title":"Ann. Transpl."},{"key":"4564_CR15","doi-asserted-by":"crossref","unstructured":"Method of the Year 2020: spatially resolved transcriptomics. Nat. Methods 18, 1 (2021).","DOI":"10.1038\/s41592-020-01042-x"},{"key":"4564_CR16","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1126\/science.1132939","volume":"313","author":"J Lamb","year":"2006","unstructured":"Lamb, J. et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313, 1929\u20131935 (2006).","journal-title":"Science"},{"key":"4564_CR17","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.cell.2007.08.021","volume":"130","author":"TW Corson","year":"2007","unstructured":"Corson, T. W. & Crews, C. M. Molecular understanding and modern application of traditional medicines: triumphs and trials. Cell 130, 769\u2013774 (2007).","journal-title":"Cell"},{"key":"4564_CR18","doi-asserted-by":"crossref","unstructured":"Venkatesha, S. H. & Moudgil, K. D. Celastrol and Its Role in Controlling Chronic Diseases in Anti-inflammatory Nutraceuticals and Chronic Diseases (eds Gupta, S. C., Prasad, S. & Aggarwal, B. B.) 267\u2013289 (Springer International Publishing, 2016).","DOI":"10.1007\/978-3-319-41334-1_12"},{"key":"4564_CR19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.lfs.2019.04.025","volume":"227","author":"H Aceros","year":"2019","unstructured":"Aceros, H. et al. Celastrol-type HSP90 modulators allow for potent cardioprotective effects. Life Sci. 227, 8\u201319 (2019).","journal-title":"Life Sci."},{"key":"4564_CR20","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.jss.2013.07.048","volume":"186","author":"C Chu","year":"2014","unstructured":"Chu, C., He, W., Kuang, Y., Ren, K. & Gou, X. Celastrol protects kidney against ischemia-reperfusion-induced injury in rats. J. Surg. Res. 186, 398\u2013407 (2014).","journal-title":"J. Surg. Res."},{"key":"4564_CR21","volume":"18","author":"DD Liu","year":"2021","unstructured":"Liu, D. D. et al. Celastrol exerts a neuroprotective effect by directly binding to HMGB1 protein in cerebral ischemia-reperfusion. J. Neuroinflammation 18, 174 (2021).","journal-title":"J. Neuroinflammation"},{"key":"4564_CR22","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1097\/00007890-199306000-00011","volume":"55","author":"S Suzuki","year":"1993","unstructured":"Suzuki, S., Toledo-Pereyra, L. H., Rodriguez, F. J. & Cejalvo, D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation 55, 1265\u20131272 (1993).","journal-title":"Transplantation"},{"key":"4564_CR23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF01454004","volume":"103","author":"K Jungermann","year":"1995","unstructured":"Jungermann, K. Zonation of metabolism and gene expression in liver. Histochem. Cell Biol. 103, 81\u201391 (1995).","journal-title":"Histochem. Cell Biol."},{"key":"4564_CR24","doi-asserted-by":"crossref","first-page":"G655","DOI":"10.1152\/ajpgi.00326.2017","volume":"314","author":"Z Lei","year":"2018","unstructured":"Lei, Z. et al. cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING. Am. J. Physiol. Gastrointest. Liver Physiol. 314, G655\u2013G667 (2018).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"4564_CR25","first-page":"142736","volume":"2015","author":"X Zhao","year":"2015","unstructured":"Zhao, X., Liang, B., Liu, Y. & Huang, X. Agaricoglycerides protect against hepatic ischemia\/reperfusion injury by attenuating inflammatory response, oxidative stress, and expression of NF-\u03baB. Evid. Based Complementary Altern. Med. 2015, 142736\u2013142736 (2015).","journal-title":"Evid. Based Complementary Altern. Med."},{"key":"4564_CR26","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.surg.2005.04.019","volume":"138","author":"M Vilatoba","year":"2005","unstructured":"Vilatoba, M. et al. Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis. Surgery 138, 342\u2013351 (2005).","journal-title":"Surgery"},{"key":"4564_CR27","doi-asserted-by":"crossref","first-page":"496","DOI":"10.2174\/138161208783597353","volume":"14","author":"C Pulitan\u00f2","year":"2008","unstructured":"Pulitan\u00f2, C. & Aldrighetti, L. The protective role of steroids in ischemia-reperfusion injury of the liver. Curr. Pharm. Des. 14, 496\u2013503 (2008).","journal-title":"Curr. Pharm. Des."},{"key":"4564_CR28","volume":"9","author":"B Readhead","year":"2018","unstructured":"Readhead, B. et al. Expression-based drug screening of neural progenitor cells from individuals with schizophrenia. Nat. Commun. 9, 4412 (2018).","journal-title":"Nat. Commun."},{"key":"4564_CR29","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrgastro.2012.225","volume":"10","author":"Y Zhai","year":"2013","unstructured":"Zhai, Y., Petrowsky, H., Hong, J. C., Busuttil, R. W. & Kupiec-Weglinski, J. W. Ischaemia-reperfusion injury in liver transplantation\u2013from bench to bedside. Nat. Rev. Gastroenterol. Hepatol. 10, 79\u201389 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"4564_CR30","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.stem.2022.04.008","volume":"29","author":"S Ben-Moshe","year":"2022","unstructured":"Ben-Moshe, S. et al. The spatiotemporal program of zonal liver regeneration following acute injury. Cell Stem Cell 29, 973\u2013989.e10 (2022).","journal-title":"Cell Stem Cell"},{"key":"4564_CR31","doi-asserted-by":"crossref","first-page":"H259","DOI":"10.1111\/j.1750-3841.2009.01330.x","volume":"74","author":"S Yan","year":"2009","unstructured":"Yan, S., Wu, S., Yin, M., Chen, H. & Chen, H. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J. Food Sci. 74, H259\u2013H265 (2009).","journal-title":"J. Food Sci."},{"key":"4564_CR32","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1039\/C6FO01329E","volume":"8","author":"A Zeb","year":"2017","unstructured":"Zeb, A. & Rahman, S. U. Protective effects of dietary glycine and glutamic acid toward the toxic effects of oxidized mustard oil in rabbits. Food Funct. 8, 429\u2013436 (2017).","journal-title":"Food Funct."},{"key":"4564_CR33","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/01.sla.0000110321.64275.95","volume":"239","author":"RJ Schauer","year":"2004","unstructured":"Schauer, R. J. et al. Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia. Ann. Surg. 239, 220\u2013231 (2004).","journal-title":"Ann. Surg."},{"key":"4564_CR34","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.3390\/ijms20092347","volume":"20","author":"T Kietzmann","year":"2019","unstructured":"Kietzmann, T. Liver zonation in health and disease: hypoxia and hypoxia-inducible transcription factors as concert masters. Int. J. Mol. Sci. 20, 2347 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"4564_CR35","doi-asserted-by":"crossref","first-page":"616","DOI":"10.20892\/j.issn.2095-3941.2021.0158","volume":"18","author":"H Sun","year":"2021","unstructured":"Sun, H. et al. Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer. Cancer Biol. Med. 18, 616\u2013630 (2021).","journal-title":"Cancer Biol. Med."},{"key":"4564_CR36","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41416-018-0368-3","volume":"120","author":"M Foltyn","year":"2019","unstructured":"Foltyn, M. et al. The physiological mTOR complex 1 inhibitor DDIT4 mediates therapy resistance in glioblastoma. Br. J. Cancer 120, 481\u2013487 (2019).","journal-title":"Br. J. Cancer"},{"key":"4564_CR37","doi-asserted-by":"crossref","first-page":"590532","DOI":"10.3389\/fimmu.2021.590532","volume":"12","author":"SR Mohapatra","year":"2021","unstructured":"Mohapatra, S. R. et al. Hypoxia routes tryptophan homeostasis towards increased tryptamine production. Front. Immunol. 12, 590532\u2013590532 (2021).","journal-title":"Front. Immunol."},{"key":"4564_CR38","doi-asserted-by":"crossref","first-page":"e1208","DOI":"10.1038\/cddis.2014.174","volume":"5","author":"S Patouraux","year":"2014","unstructured":"Patouraux, S. et al. Osteopontin deficiency aggravates hepatic injury induced by ischemia-reperfusion in mice. Cell Death Dis. 5, e1208\u2013e1208 (2014).","journal-title":"Cell Death Dis."},{"key":"4564_CR39","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1002\/jcp.22609","volume":"226","author":"K Kim","year":"2011","unstructured":"Kim, K. et al. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J. Cell. Physiol. 226, 2484\u20132493 (2011).","journal-title":"J. Cell. Physiol."},{"key":"4564_CR40","doi-asserted-by":"crossref","first-page":"109484","DOI":"10.1016\/j.cellsig.2019.109484","volume":"67","author":"S Shin","year":"2020","unstructured":"Shin, S., Gombedza, F. C. & Bandyopadhyay, B. C. l-ornithine activates Ca(2+) signaling to exert its protective function on human proximal tubular cells. Cell Signal 67, 109484 (2020).","journal-title":"Cell Signal"},{"key":"4564_CR41","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/hep.1840160226","volume":"16","author":"T Ikeda","year":"1992","unstructured":"Ikeda, T. et al. Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats. Hepatology 16, 454\u2013461 (1992).","journal-title":"Hepatology"},{"key":"4564_CR42","doi-asserted-by":"crossref","first-page":"408","DOI":"10.3390\/biology10050408","volume":"10","author":"V Natarajan","year":"2021","unstructured":"Natarajan, V., Moeun, Y. & Kidambi, S. Exploring interactions between primary hepatocytes and non-parenchymal cells on physiological and pathological liver stiffness. Biology 10, 408 (2021).","journal-title":"Biology"},{"key":"4564_CR43","doi-asserted-by":"crossref","first-page":"G991","DOI":"10.1152\/ajpgi.00231.2018","volume":"315","author":"JR Klune","year":"2018","unstructured":"Klune, J. R. et al. IL-23 mediates murine liver transplantation ischemia-reperfusion injury via IFN-\u03b3\/IRF-1 pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 315, G991\u2013G1002 (2018).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"4564_CR44","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.jhep.2020.06.004","volume":"73","author":"A Saviano","year":"2020","unstructured":"Saviano, A., Henderson, N. C. & Baumert, T. F. Single-cell genomics and spatial transcriptomics: discovery of novel cell states and cellular interactions in liver physiology and disease biology. J. Hepatol. 73, 1219\u20131230 (2020).","journal-title":"J. Hepatol."},{"key":"4564_CR45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/002215540104900112","volume":"49","author":"E Taniguchi","year":"2001","unstructured":"Taniguchi, E., Sakisaka, S., Matsuo, K., Tanikawa, K. & Sata, M. Expression and role of vascular endothelial growth factor in liver regeneration after partial hepatectomy in rats. J. Histochem. Cytochem. 49, 121\u2013129 (2001).","journal-title":"J. Histochem. Cytochem."},{"key":"4564_CR46","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/mt.2008.237","volume":"17","author":"L Devey","year":"2009","unstructured":"Devey, L. et al. Tissue-resident macrophages protect the liver from ischemia reperfusion injury via a heme oxygenase-1-dependent mechanism. Mol. Ther. 17, 65\u201372 (2009).","journal-title":"Mol. Ther."},{"key":"4564_CR47","doi-asserted-by":"crossref","first-page":"7413","DOI":"10.3748\/wjg.v12.i46.7413","volume":"12","author":"G Kolios","year":"2006","unstructured":"Kolios, G., Valatas, V. & Kouroumalis, E. Role of Kupffer cells in the pathogenesis of liver disease. World J. Gastroenterol. 12, 7413\u20137420 (2006).","journal-title":"World J. Gastroenterol."},{"key":"4564_CR48","doi-asserted-by":"crossref","first-page":"101859","DOI":"10.1016\/j.redox.2021.101859","volume":"40","author":"S Li","year":"2021","unstructured":"Li, S. et al. The protective effects of fibroblast growth factor 10 against hepatic ischemia-reperfusion injury in mice. Redox Biol. 40, 101859 (2021).","journal-title":"Redox Biol."},{"key":"4564_CR49","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.intimp.2014.01.006","volume":"19","author":"M Feng","year":"2014","unstructured":"Feng, M. et al. Adoptive transfer of hepatic stellate cells ameliorates liver ischemia reperfusion injury through enriching regulatory T cells. Int. Immunopharmacol. 19, 267\u2013274 (2014).","journal-title":"Int. Immunopharmacol."},{"key":"4564_CR50","doi-asserted-by":"crossref","first-page":"G471","DOI":"10.1152\/ajpgi.00153.2017","volume":"314","author":"T Konishi","year":"2018","unstructured":"Konishi, T., Schuster, R. M. & Lentsch, A. B. Proliferation of hepatic stellate cells, mediated by YAP and TAZ, contributes to liver repair and regeneration after liver ischemia-reperfusion injury. Am. J. Physiol. Gastrointest. Liver Physiol. 314, G471\u2013G482 (2018).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"4564_CR51","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41575-020-00411-3","volume":"18","author":"J Gracia-Sancho","year":"2021","unstructured":"Gracia-Sancho, J., Caparr\u00f3s, E., Fern\u00e1ndez-Iglesias, A. & Franc\u00e9s, R. Role of liver sinusoidal endothelial cells in liver diseases. Nat. Rev. Gastroenterol. Hepatol. 18, 411\u2013431 (2021).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"4564_CR52","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41419-021-03878-3","volume":"12","author":"L Wang","year":"2021","unstructured":"Wang, L. et al. Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution. Cell Death Dis. 12, 589 (2021).","journal-title":"Cell Death Dis."},{"key":"4564_CR53","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.4049\/jimmunol.1900053","volume":"204","author":"L Zheng","year":"2020","unstructured":"Zheng, L., Ling, W., Zhu, D., Li, Z. & Kong, L. Roquin-1 regulates macrophage immune response and participates in hepatic ischemia\u2013reperfusion injury. J. Immunol. 204, 1322 (2020).","journal-title":"J. Immunol."},{"key":"4564_CR54","doi-asserted-by":"crossref","first-page":"e08698","DOI":"10.7554\/eLife.08698","volume":"4","author":"RR Ramiscal","year":"2015","unstructured":"Ramiscal, R. R. et al. Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation. eLife 4, e08698 (2015).","journal-title":"eLife"},{"key":"4564_CR55","first-page":"61","volume":"2","author":"J Yang","year":"2019","unstructured":"Yang, J., Shakil, F. & Cho, S. Peripheral mechanisms of remote ischemic conditioning. Cond. Med. 2, 61\u201368 (2019).","journal-title":"Cond. Med."},{"key":"4564_CR56","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41368-018-0015-0","volume":"10","author":"K Hirai","year":"2018","unstructured":"Hirai, K., Furusho, H., Hirota, K. & Sasaki, H. Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss. Int. J. Oral. Sci. 10, 12 (2018).","journal-title":"Int. J. Oral. Sci."},{"key":"4564_CR57","doi-asserted-by":"crossref","first-page":"10892","DOI":"10.1074\/jbc.M800102200","volume":"283","author":"H Zhang","year":"2008","unstructured":"Zhang, H. et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J. Biol. Chem. 283, 10892\u201310903 (2008).","journal-title":"J. Biol. Chem."},{"key":"4564_CR58","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-36063-2","volume":"8","author":"E Delbrel","year":"2018","unstructured":"Delbrel, E. et al. HIF-1\u03b1 triggers ER stress and CHOP-mediated apoptosis in alveolar epithelial cells, a key event in pulmonary fibrosis. Sci. Rep. 8, 17939 (2018).","journal-title":"Sci. Rep."},{"key":"4564_CR59","doi-asserted-by":"crossref","first-page":"bbac261","DOI":"10.1093\/bib\/bbac261","volume":"23","author":"J Li","year":"2022","unstructured":"Li, J. et al. Hiplot: a comprehensive and easy-to-use web service for boosting publication-ready biomedical data visualization. Brief. Bioinform. 23, bbac261 (2022).","journal-title":"Brief. Bioinform."},{"key":"4564_CR60","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284\u2013287 (2012).","journal-title":"OMICS"},{"key":"4564_CR61","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","volume":"36","author":"SX Ge","year":"2020","unstructured":"Ge, S. X., Jung, D. & Yao, R. ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics 36, 2628\u20132629 (2020).","journal-title":"Bioinformatics"},{"key":"4564_CR62","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-28020-5","volume":"13","author":"P Danaher","year":"2022","unstructured":"Danaher, P. et al. Advances in mixed cell deconvolution enable quantification of cell types in spatial transcriptomic data. Nat. Commun. 13, 385 (2022).","journal-title":"Nat. Commun."},{"key":"4564_CR63","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.cell.2018.02.001","volume":"172","author":"X Han","year":"2018","unstructured":"Han, X. et al. Mapping the mouse cell atlas by microwell-seq. Cell 172, 1091\u20131107.e17 (2018).","journal-title":"Cell"},{"key":"4564_CR64","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.molp.2020.06.009","volume":"13","author":"C Chen","year":"2020","unstructured":"Chen, C. et al. TBtools: an integrative toolkit developed for interactive analyses of big biological data. Mol. Plant 13, 1194\u20131202 (2020).","journal-title":"Mol. Plant"},{"key":"4564_CR65","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","volume":"6","author":"J Ru","year":"2014","unstructured":"Ru, J. et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminformatics 6, 13 (2014).","journal-title":"J. Cheminformatics"},{"key":"4564_CR66","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28, 235\u2013242 (2000).","journal-title":"Nucleic Acids Res."},{"key":"4564_CR67","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41401-019-0228-6","volume":"41","author":"Y Liu","year":"2020","unstructured":"Liu, Y. et al. CB-Dock: a web server for cavity detection-guided protein-ligand blind docking. Acta Pharm. Sin. 41, 138\u2013144 (2020).","journal-title":"Acta Pharm. Sin."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-04564-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-04564-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-04564-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T11:59:12Z","timestamp":1676721552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-04564-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,18]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4564"],"URL":"https:\/\/doi.org\/10.1038\/s42003-023-04564-0","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,18]]},"assertion":[{"value":"28 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"194"}}