{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:24:00Z","timestamp":1792160640651,"version":"4.4.0"},"reference-count":100,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Microbiol"],"DOI":"10.1038\/s41564-025-02050-3","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T09:02:51Z","timestamp":1752483771000},"page":"2073-2091","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A single-cell transcriptomic atlas reveals senescence and inflammation in the post-tuberculosis human lung"],"prefix":"10.1038","volume":"10","author":[{"given":"Guoqiang","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-9625","authenticated-orcid":false,"given":"Kuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Ping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-7727","authenticated-orcid":false,"given":"Junping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danlu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8885-5104","authenticated-orcid":false,"given":"Weiqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-889X","authenticated-orcid":false,"given":"Weihong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-0197","authenticated-orcid":false,"given":"Xiu-Wu","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3988-5067","authenticated-orcid":false,"given":"Jing","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-0612","authenticated-orcid":false,"given":"Si","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-0535","authenticated-orcid":false,"given":"Huaiyong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9289-8177","authenticated-orcid":false,"given":"Guang-Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"2050_CR1","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1016\/S0140-6736(19)30308-3","volume":"393","author":"J Furin","year":"2019","unstructured":"Furin, J., Cox, H. & Pai, M. Tuberculosis. Lancet 393, 1642\u20131656 (2019).","journal-title":"Lancet"},{"key":"2050_CR2","unstructured":"Jilani, T. N., Avula, A., Zafar Gondal, A. & Siddiqui, A. H. Active Tuberculosis (StatPearls Publishing, 2025)."},{"key":"2050_CR3","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.tube.2011.03.007","volume":"91","author":"RL Hunter","year":"2011","unstructured":"Hunter, R. L. Pathology of post primary tuberculosis of the lung: an illustrated critical review. Tuberculosis 91, 497\u2013509 (2011).","journal-title":"Tuberculosis"},{"key":"2050_CR4","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ijid.2014.12.016","volume":"32","author":"AL Byrne","year":"2015","unstructured":"Byrne, A. L., Marais, B. J., Mitnick, C. D., Lecca, L. & Marks, G. B. Tuberculosis and chronic respiratory disease: a systematic review. Int. J. Infect. Dis. 32, 138\u2013146 (2015).","journal-title":"Int. J. Infect. Dis."},{"key":"2050_CR5","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.chom.2018.08.001","volume":"24","author":"SB Cohen","year":"2018","unstructured":"Cohen, S. B. et al. Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe 24, 439\u2013446.e4 (2018).","journal-title":"Cell Host Microbe"},{"key":"2050_CR6","doi-asserted-by":"publisher","first-page":"170077","DOI":"10.1183\/16000617.0077-2017","volume":"27","author":"S Ravimohan","year":"2018","unstructured":"Ravimohan, S., Kornfeld, H., Weissman, D. & Bisson, G. P. Tuberculosis and lung damage: from epidemiology to pathophysiology. Eur. Respir. Rev. 27, 170077 (2018).","journal-title":"Eur. Respir. Rev."},{"key":"2050_CR7","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3389\/fcimb.2018.00158","volume":"8","author":"Q Chai","year":"2018","unstructured":"Chai, Q., Zhang, Y. & Liu, C. H. Mycobacterium tuberculosis: an adaptable pathogen associated with multiple human diseases. Front. Cell. Infect. Microbiol. 8, 158 (2018).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"2050_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-10-259","volume":"10","author":"JG Pasipanodya","year":"2010","unstructured":"Pasipanodya, J. G. et al. Pulmonary impairment after tuberculosis and its contribution to TB burden. BMC Public Health 10, 259 (2010).","journal-title":"BMC Public Health"},{"key":"2050_CR9","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1093\/lifemedi\/lnac047","volume":"1","author":"H Li","year":"2022","unstructured":"Li, H. et al. Peripheral immune landscape and natural killer-like B cells in human Vogt-Koyanagi-Harada disease. Life Med. 1, 387\u2013400 (2022).","journal-title":"Life Med."},{"key":"2050_CR10","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1161\/CIRCULATIONAHA.120.052318","volume":"144","author":"JC Schupp","year":"2021","unstructured":"Schupp, J. C. et al. Integrated single-cell atlas of endothelial cells of the human lung. Circulation 144, 286\u2013302 (2021).","journal-title":"Circulation"},{"key":"2050_CR11","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1056\/NEJMoa2015432","volume":"383","author":"M Ackermann","year":"2020","unstructured":"Ackermann, M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N. Engl. J. Med. 383, 120\u2013128 (2020).","journal-title":"N. Engl. J. Med."},{"key":"2050_CR12","doi-asserted-by":"crossref","first-page":"lnac021","DOI":"10.1093\/lifemedi\/lnac021","volume":"2","author":"AB Consortium","year":"2023","unstructured":"Consortium, A. B. et al. A framework of biomarkers for vascular aging: a consensus statement by the Aging Biomarker Consortium. Life Med. 2, lnac021 (2023).","journal-title":"Life Med."},{"key":"2050_CR13","doi-asserted-by":"publisher","first-page":"lnac021","DOI":"10.1093\/lifemedi\/lnac021","volume":"2","author":"D Wang","year":"2022","unstructured":"Wang, D. et al. Chimeric blood vessels sustained development of the xenogeneic antler: a unique model for xenogeneic organ generation. Life Med. 2, lnac021 (2022).","journal-title":"Life Med."},{"key":"2050_CR14","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1038\/nri2171","volume":"7","author":"JS Pober","year":"2007","unstructured":"Pober, J. S. & Sessa, W. C. Evolving functions of endothelial cells in inflammation. Nat. Rev. Immunol. 7, 803\u2013815 (2007).","journal-title":"Nat. Rev. Immunol."},{"key":"2050_CR15","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1038\/s41591-023-02327-2","volume":"29","author":"L Sikkema","year":"2023","unstructured":"Sikkema, L. et al. An integrated cell atlas of the lung in health and disease. Nat. Med. 29, 1563\u20131577 (2023).","journal-title":"Nat. Med."},{"key":"2050_CR16","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1038\/s41556-021-00796-6","volume":"23","author":"S Wang","year":"2021","unstructured":"Wang, S. et al. A single-cell transcriptomic landscape of the lungs of patients with COVID-19. Nat. Cell Biol. 23, 1314\u20131328 (2021).","journal-title":"Nat. Cell Biol."},{"key":"2050_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26603-2","volume":"12","author":"S Lee","year":"2021","unstructured":"Lee, S. et al. Molecular programs of fibrotic change in aging human lung. Nat. Commun. 12, 6309 (2021).","journal-title":"Nat. Commun."},{"key":"2050_CR18","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41586-022-04541-3","volume":"604","author":"P Kadur Lakshminarasimha Murthy","year":"2022","unstructured":"Kadur Lakshminarasimha Murthy, P. et al. Human distal lung maps and lineage hierarchies reveal a bipotent progenitor. Nature 604, 111\u2013119 (2022).","journal-title":"Nature"},{"key":"2050_CR19","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1038\/s41591-018-0096-5","volume":"24","author":"D Lambrechts","year":"2018","unstructured":"Lambrechts, D. et al. Phenotype molding of stromal cells in the lung tumor microenvironment. Nat. Med. 24, 1277\u20131289 (2018).","journal-title":"Nat. Med."},{"key":"2050_CR20","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1093\/lifemedi\/lnac002","volume":"1","author":"F Zhang","year":"2022","unstructured":"Zhang, F. et al. Single-cell atlas of multilineage cardiac organoids derived from human induced pluripotent stem cells. Life Med. 1, 179\u2013195 (2022).","journal-title":"Life Med."},{"key":"2050_CR21","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1007\/s11427-023-2305-0","volume":"66","author":"Aging Biomarker Consortium","year":"2023","unstructured":"Aging Biomarker Consortium et al. Biomarkers of aging. Sci. China Life Sci. 66, 893\u20131066 (2023).","journal-title":"Sci. China Life Sci."},{"key":"2050_CR22","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1007\/s11427-022-2161-3","volume":"65","author":"Y Cai","year":"2022","unstructured":"Cai, Y. et al. The landscape of aging. Sci. China Life Sci. 65, 2354\u20132454 (2022).","journal-title":"Sci. China Life Sci."},{"key":"2050_CR23","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/nri.2017.69","volume":"17","author":"AM Cadena","year":"2017","unstructured":"Cadena, A. M., Fortune, S. M. & Flynn, J. L. Heterogeneity in tuberculosis. Nat. Rev. Immunol. 17, 691\u2013702 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"2050_CR24","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1210\/me.2012-1035","volume":"26","author":"B Wang","year":"2012","unstructured":"Wang, B., Parobchak, N. & Rosen, T. RelB\/NF-kappaB2 regulates corticotropin-releasing hormone in the human placenta. Mol. Endocrinol. 26, 1356\u20131369 (2012).","journal-title":"Mol. Endocrinol."},{"key":"2050_CR25","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12706","volume":"53","author":"Q Tang","year":"2020","unstructured":"Tang, Q. et al. Withaferin A triggers G2\/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4-ATF3-CHOP axis. Cell Prolif. 53, e12706 (2020).","journal-title":"Cell Prolif."},{"key":"2050_CR26","doi-asserted-by":"publisher","first-page":"e137427","DOI":"10.1172\/jci.insight.137427","volume":"5","author":"DJ Garay-Baquero","year":"2020","unstructured":"Garay-Baquero, D. J. et al. Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis. JCI Insight 5, e137427 (2020).","journal-title":"JCI Insight"},{"key":"2050_CR27","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1074\/jbc.M204360200","volume":"278","author":"MP Bernimoulin","year":"2003","unstructured":"Bernimoulin, M. P. et al. Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51. J. Biol. Chem. 278, 37\u201347 (2003).","journal-title":"J. Biol. Chem."},{"key":"2050_CR28","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1002\/cbic.201700220","volume":"18","author":"S Wedepohl","year":"2017","unstructured":"Wedepohl, S. et al. Reducing macro- and microheterogeneity of N-glycans enables the crystal structure of the lectin and EGF-like domains of human l-selectin to be solved at 1.9 \u00c5 resolution. ChemBioChem 18, 1338\u20131345 (2017).","journal-title":"ChemBioChem"},{"key":"2050_CR29","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.1074\/jbc.M116.767186","volume":"292","author":"P Mehta-D\u2019souza","year":"2017","unstructured":"Mehta-D\u2019souza, P. et al. Glycan bound to the selectin low affinity state engages Glu-88 to stabilize the high affinity state under force. J. Biol. Chem. 292, 2510\u20132518 (2017).","journal-title":"J. Biol. Chem."},{"key":"2050_CR30","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1164\/rccm.201611-2263OC","volume":"196","author":"HB Schiller","year":"2017","unstructured":"Schiller, H. B. et al. Deep proteome profiling reveals common prevalence of MZB1-positive plasma B cells in human lung and skin fibrosis. Am. J. Respir. Crit. Care Med. 196, 1298\u20131310 (2017).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2050_CR31","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.celrep.2018.06.042","volume":"24","author":"D Pajuelo","year":"2018","unstructured":"Pajuelo, D. et al. NAD+ depletion triggers macrophage necroptosis, a cell death pathway exploited by Mycobacterium tuberculosis. Cell Rep. 24, 429\u2013440 (2018).","journal-title":"Cell Rep."},{"key":"2050_CR32","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.cell.2019.08.004","volume":"178","author":"FJ Roca","year":"2019","unstructured":"Roca, F. J., Whitworth, L. J., Redmond, S., Jones, A. A. & Ramakrishnan, L. TNF induces pathogenic programmed macrophage necrosis in tuberculosis through a mitochondrial-lysosomal-endoplasmic reticulum circuit. Cell 178, 1344\u20131361.e11 (2019).","journal-title":"Cell"},{"key":"2050_CR33","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/cmi.2017.88","volume":"14","author":"CH Liu","year":"2017","unstructured":"Liu, C. H., Liu, H. & Ge, B. Innate immunity in tuberculosis: host defense vs pathogen evasion. Cell. Mol. Immunol. 14, 963\u2013975 (2017).","journal-title":"Cell. Mol. Immunol."},{"key":"2050_CR34","doi-asserted-by":"publisher","first-page":"7025","DOI":"10.1016\/j.cell.2024.10.019","volume":"187","author":"S Ma","year":"2024","unstructured":"Ma, S. et al. Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging. Cell 187, 7025\u20137044.e34 (2024).","journal-title":"Cell"},{"key":"2050_CR35","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1093\/lifemedi\/lnac006","volume":"1","author":"C Li","year":"2022","unstructured":"Li, C., Ying, T., Dimitrov, D. S. & Wu, Y. Counter changes with changelessness: cope with SARS-CoV-2 immune evasion by targeting cryptic epitopes. Life Med. 1, 24\u201326 (2022).","journal-title":"Life Med."},{"key":"2050_CR36","doi-asserted-by":"publisher","first-page":"lnad023","DOI":"10.1093\/lifemedi\/lnad023","volume":"2","author":"X Liang","year":"2023","unstructured":"Liang, X., Wang, Y. & Guo, T. Proteomics approaches to long COVID: status and outlooks. Life Med. 2, lnad023 (2023).","journal-title":"Life Med."},{"key":"2050_CR37","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1093\/lifemedi\/lnac011","volume":"1","author":"X Xiao","year":"2022","unstructured":"Xiao, X., Tong, L., Bogan, J. S., Wang, P. & Cheng, G. Diabetes and COVID-19, a link revealed. Life Med. 1, 64\u201366 (2022).","journal-title":"Life Med."},{"key":"2050_CR38","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1038\/s41590-020-0762-x","volume":"21","author":"JY Zhang","year":"2020","unstructured":"Zhang, J. Y. et al. Single-cell landscape of immunological responses in patients with COVID-19. Nat. Immunol. 21, 1107\u20131118 (2020).","journal-title":"Nat. Immunol."},{"key":"2050_CR39","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/s41577-021-00646-4","volume":"22","author":"DA Mogilenko","year":"2022","unstructured":"Mogilenko, D. A., Shchukina, I. & Artyomov, M. N. Immune ageing at single-cell resolution. Nat. Rev. Immunol. 22, 484\u2013498 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"2050_CR40","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/lifemedi\/lnac013","volume":"1","author":"SX Leng","year":"2022","unstructured":"Leng, S. X. & Pawelec, G. Single-cell immune atlas for human aging and frailty. Life Med. 1, 67\u201370 (2022).","journal-title":"Life Med."},{"key":"2050_CR41","doi-asserted-by":"publisher","first-page":"D1047","DOI":"10.1093\/nar\/gkae1102","volume":"53","author":"H Li","year":"2025","unstructured":"Li, H. et al. Immunosenescence inventory\u2014a multi-omics database for immune aging research. Nucleic Acids Res. 53, D1047\u2013D1054 (2025).","journal-title":"Nucleic Acids Res."},{"key":"2050_CR42","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.cell.2022.12.017","volume":"186","author":"X Liu","year":"2023","unstructured":"Liu, X. et al. Resurrection of endogenous retroviruses during aging reinforces senescence. Cell 186, 287\u2013304.e26 (2023).","journal-title":"Cell"},{"key":"2050_CR43","doi-asserted-by":"publisher","first-page":"6001","DOI":"10.1093\/nar\/gkaa425","volume":"48","author":"H Hu","year":"2020","unstructured":"Hu, H. et al. ZKSCAN3 counteracts cellular senescence by stabilizing heterochromatin. Nucleic Acids Res. 48, 6001\u20136018 (2020).","journal-title":"Nucleic Acids Res."},{"key":"2050_CR44","doi-asserted-by":"publisher","first-page":"D825","DOI":"10.1093\/nar\/gkaa894","volume":"49","author":"Aging Atlas","year":"2021","unstructured":"Aging Atlas Consortium. Aging Atlas: a multi-omics database for aging biology. Nucleic Acids Res. 49, D825\u2013D830 (2021).","journal-title":"Nucleic Acids Res."},{"key":"2050_CR45","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.immuni.2010.05.007","volume":"32","author":"S Gordon","year":"2010","unstructured":"Gordon, S. & Martinez, F. O. Alternative activation of macrophages: mechanism and functions. Immunity 32, 593\u2013604 (2010).","journal-title":"Immunity"},{"key":"2050_CR46","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018101233","volume":"38","author":"R Rauschmeier","year":"2019","unstructured":"Rauschmeier, R. et al. Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity. EMBO J. 38, e101233 (2019).","journal-title":"EMBO J."},{"key":"2050_CR47","doi-asserted-by":"publisher","first-page":"701279","DOI":"10.3389\/fcvm.2021.701279","volume":"8","author":"J Li","year":"2021","unstructured":"Li, J., Zhou, L., Ouyang, X. & He, P. Transcription factor-7-like-2 (TCF7L2) in atherosclerosis: a potential biomarker and therapeutic target. Front. Cardiovasc. Med. 8, 701279 (2021).","journal-title":"Front. Cardiovasc. Med."},{"key":"2050_CR48","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1164\/rccm.201810-1972OC","volume":"200","author":"G Chen","year":"2019","unstructured":"Chen, G. et al. XBP1S regulates MUC5B in a promoter variant-dependent pathway in idiopathic pulmonary fibrosis airway epithelia. Am. J. Respir. Crit. Care Med. 200, 220\u2013234 (2019).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2050_CR49","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.chest.2017.11.008","volume":"154","author":"J Ma","year":"2018","unstructured":"Ma, J., Rubin, B. K. & Voynow, J. A. Mucins, mucus, and goblet cells. Chest 154, 169\u2013176 (2018).","journal-title":"Chest"},{"key":"2050_CR50","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1083\/jcb.201110131","volume":"197","author":"S Wang","year":"2012","unstructured":"Wang, S. & Kaufman, R. J. The impact of the unfolded protein response on human disease. J. Cell Biol. 197, 857\u2013867 (2012).","journal-title":"J. Cell Biol."},{"key":"2050_CR51","doi-asserted-by":"publisher","first-page":"e0198703","DOI":"10.1371\/journal.pone.0198703","volume":"13","author":"CY Chen","year":"2018","unstructured":"Chen, C. Y. et al. Examining the role of the surfactant family member SFTA3 in interneuron specification. PLoS ONE 13, e0198703 (2018).","journal-title":"PLoS ONE"},{"key":"2050_CR52","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1164\/rccm.201910-1977OC","volume":"203","author":"MS Espindola","year":"2021","unstructured":"Espindola, M. S. et al. Differential responses to targeting matrix metalloproteinase 9 in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 203, 458\u2013470 (2021).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2050_CR53","doi-asserted-by":"publisher","first-page":"8813","DOI":"10.7150\/thno.62521","volume":"11","author":"SK Hsu","year":"2021","unstructured":"Hsu, S. K. et al. Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment. Theranostics 11, 8813\u20138835 (2021).","journal-title":"Theranostics"},{"key":"2050_CR54","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1002\/j.2040-4603.2015.tb00615.x","volume":"5","author":"NM Goldenberg","year":"2015","unstructured":"Goldenberg, N. M. & Kuebler, W. M. Endothelial cell regulation of pulmonary vascular tone, inflammation, and coagulation. Compr. Physiol. 5, 531\u2013559 (2015).","journal-title":"Compr. Physiol."},{"key":"2050_CR55","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1164\/rccm.201910-1911TR","volume":"202","author":"J Joffre","year":"2020","unstructured":"Joffre, J., Hellman, J., Ince, C. & Ait-Oufella, H. Endothelial responses in sepsis. Am. J. Respir. Crit. Care Med. 202, 361\u2013370 (2020).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2050_CR56","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","volume":"21","author":"A Decout","year":"2021","unstructured":"Decout, A., Katz, J. D., Venkatraman, S. & Ablasser, A. The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nat. Rev. Immunol. 21, 548\u2013569 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"2050_CR57","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/s41423-020-0502-z","volume":"17","author":"Q Chai","year":"2020","unstructured":"Chai, Q., Wang, L., Liu, C. H. & Ge, B. New insights into the evasion of host innate immunity by Mycobacterium tuberculosis. Cell. Mol. Immunol. 17, 901\u2013913 (2020).","journal-title":"Cell. Mol. Immunol."},{"key":"2050_CR58","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1042\/CS20130676","volume":"127","author":"SE Cheng","year":"2014","unstructured":"Cheng, S. E., Lee, I. T., Lin, C. C., Hsiao, L. D. & Yang, C. M. Thrombin induces ICAM-1 expression in human lung epithelial cells via c-Src\/PDGFR\/PI3K\/Akt-dependent NF-kappaB\/p300 activation. Clin. Sci. 127, 171\u2013183 (2014).","journal-title":"Clin. Sci."},{"key":"2050_CR59","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1161\/01.ATV.0000099880.09014.7D","volume":"24","author":"T Minami","year":"2004","unstructured":"Minami, T. et al. Thrombin and phenotypic modulation of the endothelium. Arterioscler. Thromb. Vasc. Biol. 24, 41\u201353 (2004).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2050_CR60","doi-asserted-by":"publisher","first-page":"5637","DOI":"10.4049\/jimmunol.1501758","volume":"195","author":"MG Thompson","year":"2015","unstructured":"Thompson, M. G. et al. FOXO3-NF-kappaB RelA protein complexes reduce proinflammatory cell signaling and function. J. Immunol. 195, 5637\u20135647 (2015).","journal-title":"J. Immunol."},{"key":"2050_CR61","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1097\/HEP.0000000000000401","volume":"78","author":"R Maeso-Diaz","year":"2023","unstructured":"Maeso-Diaz, R. et al. Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression. Hepatology 78, 1209\u20131222 (2023).","journal-title":"Hepatology"},{"key":"2050_CR62","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1210\/me.2011-1187","volume":"26","author":"Y Cheng","year":"2012","unstructured":"Cheng, Y. et al. Intraovarian thrombin and activated protein C signaling system regulates steroidogenesis during the periovulatory period. Mol. Endocrinol. 26, 331\u2013340 (2012).","journal-title":"Mol. Endocrinol."},{"key":"2050_CR63","doi-asserted-by":"publisher","first-page":"2758","DOI":"10.1016\/j.celrep.2020.01.108","volume":"30","author":"KA Ngo","year":"2020","unstructured":"Ngo, K. A. et al. Dissecting the regulatory strategies of NF-kappaB RelA target genes in the inflammatory response reveals differential transactivation logics. Cell Rep. 30, 2758\u20132775.e6 (2020).","journal-title":"Cell Rep."},{"key":"2050_CR64","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1084\/jem.189.6.999","volume":"189","author":"F Ouaaz","year":"1999","unstructured":"Ouaaz, F., Li, M. & Beg, A. A. A critical role for the RelA subunit of nuclear factor kappaB in regulation of multiple immune-response genes and in Fas-induced cell death. J. Exp. Med. 189, 999\u20131004 (1999).","journal-title":"J. Exp. Med."},{"key":"2050_CR65","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1038\/s41590-023-01561-7","volume":"24","author":"M Zhao","year":"2023","unstructured":"Zhao, M. et al. NF-kappaB subunits direct kinetically distinct transcriptional cascades in antigen receptor-activated B cells. Nat. Immunol. 24, 1552\u20131564 (2023).","journal-title":"Nat. Immunol."},{"key":"2050_CR66","doi-asserted-by":"publisher","first-page":"e20210615","DOI":"10.1084\/jem.20210615","volume":"218","author":"D Pisu","year":"2021","unstructured":"Pisu, D. et al. Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung. J. Exp. Med. 218, e20210615 (2021).","journal-title":"J. Exp. Med."},{"key":"2050_CR67","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.chom.2020.11.013","volume":"29","author":"E Esaulova","year":"2021","unstructured":"Esaulova, E. et al. The immune landscape in tuberculosis reveals populations linked to disease and latency. Cell Host Microbe 29, 165\u2013178.e8 (2021).","journal-title":"Cell Host Microbe"},{"key":"2050_CR68","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1146\/annurev-immunol-093019-010426","volume":"39","author":"MM Ravesloot-Chavez","year":"2021","unstructured":"Ravesloot-Chavez, M. M., Van Dis, E. & Stanley, S. A. The innate immune response to Mycobacterium tuberculosis infection. Annu. Rev. Immunol. 39, 611\u2013637 (2021).","journal-title":"Annu. Rev. Immunol."},{"key":"2050_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15997-0","volume":"11","author":"W Zhang","year":"2020","unstructured":"Zhang, W. et al. A single-cell transcriptomic landscape of primate arterial aging. Nat. Commun. 11, 2202 (2020).","journal-title":"Nat. Commun."},{"key":"2050_CR70","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/procel\/pwaf004","volume":"16","author":"F Zheng","year":"2025","unstructured":"Zheng, F. et al. FOXO3-engineered human mesenchymal stem cells efficiently enhance post-ischemic stroke functional rehabilitation. Protein Cell 16, 365\u2013373 (2025).","journal-title":"Protein Cell"},{"key":"2050_CR71","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1056\/NEJMoa1109719","volume":"366","author":"P Tricoci","year":"2012","unstructured":"Tricoci, P. et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N. Engl. J. Med. 366, 20\u201333 (2012).","journal-title":"N. Engl. J. Med."},{"key":"2050_CR72","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.cell.2020.07.017","volume":"182","author":"A Maynard","year":"2020","unstructured":"Maynard, A. et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell 182, 1232\u20131251.e22 (2020).","journal-title":"Cell"},{"key":"2050_CR73","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41422-020-00455-9","volume":"31","author":"E Wauters","year":"2021","unstructured":"Wauters, E. et al. Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages. Cell Res. 31, 272\u2013290 (2021).","journal-title":"Cell Res."},{"key":"2050_CR74","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1007\/s13238-018-0560-5","volume":"9","author":"P Wang","year":"2018","unstructured":"Wang, P. et al. CRISPR\/Cas9-mediated gene knockout reveals a guardian role of NF-kappaB\/RelA in maintaining the homeostasis of human vascular cells. Protein Cell 9, 945\u2013965 (2018).","journal-title":"Protein Cell"},{"key":"2050_CR75","doi-asserted-by":"publisher","first-page":"6358","DOI":"10.1016\/j.cell.2024.08.021","volume":"187","author":"Y Yang","year":"2024","unstructured":"Yang, Y. et al. Metformin decelerates aging clock in male monkeys. Cell 187, 6358\u20136378.e29 (2024).","journal-title":"Cell"},{"key":"2050_CR76","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1093\/procel\/pwad060","volume":"15","author":"F Liu","year":"2024","unstructured":"Liu, F. et al. Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling. Protein Cell 15, 441\u2013459 (2024).","journal-title":"Protein Cell"},{"key":"2050_CR77","doi-asserted-by":"publisher","unstructured":"Wang, M. et al. Single-nucleus transcriptomics decodes the link between aging and lumbar disc herniation. Protein Cell https:\/\/doi.org\/10.1093\/procel\/pwaf025 (2025).","DOI":"10.1093\/procel\/pwaf025"},{"key":"2050_CR78","first-page":"180","volume":"14","author":"G Sun","year":"2023","unstructured":"Sun, G. et al. Single-cell transcriptomic atlas of mouse cochlear aging. Protein Cell 14, 180\u2013201 (2023).","journal-title":"Protein Cell"},{"key":"2050_CR79","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1007\/s13238-020-00740-8","volume":"11","author":"F Wang","year":"2020","unstructured":"Wang, F. et al. Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing. Protein Cell 11, 809\u2013824 (2020).","journal-title":"Protein Cell"},{"key":"2050_CR80","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.cell.2020.01.009","volume":"180","author":"S Wang","year":"2020","unstructured":"Wang, S. et al. Single-cell transcriptomic atlas of primate ovarian aging. Cell 180, 585\u2013600.e19 (2020).","journal-title":"Cell"},{"key":"2050_CR81","doi-asserted-by":"crossref","unstructured":"Lu, H. et al. Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics. Protein Cell 15, 364\u2013384 (2023).","DOI":"10.1093\/procel\/pwad063"},{"key":"2050_CR82","doi-asserted-by":"crossref","unstructured":"Wang, C. et al. RIG-I-driven CDKN1A stabilization reinforces cellular senescence. Sci. China Life Sci. 68, 1646\u20131661 (2025).","DOI":"10.1007\/s11427-024-2844-8"},{"key":"2050_CR83","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1007\/s13238-021-00860-9","volume":"13","author":"J Lei","year":"2022","unstructured":"Lei, J. et al. Exosomes from antler stem cells alleviate mesenchymal stem cell senescence and osteoarthritis. Protein Cell 13, 220\u2013226 (2022).","journal-title":"Protein Cell"},{"key":"2050_CR84","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/cr.2017.18","volume":"27","author":"R Ren","year":"2017","unstructured":"Ren, R. et al. Visualization of aging-associated chromatin alterations with an engineered TALE system. Cell Res. 27, 483\u2013504 (2017).","journal-title":"Cell Res."},{"key":"2050_CR85","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357\u2013360 (2015).","journal-title":"Nat. Methods"},{"key":"2050_CR86","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"2050_CR87","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"CS McGinnis","year":"2019","unstructured":"McGinnis, C. S., Murrow, L. M. & Gartner, Z. J. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 8, 329\u2013337.e4 (2019).","journal-title":"Cell Syst."},{"key":"2050_CR88","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289\u20131296 (2019).","journal-title":"Nat. Methods"},{"key":"2050_CR89","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).","journal-title":"Nat. Commun."},{"key":"2050_CR90","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"2050_CR91","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar, S. et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14, 1083\u20131086 (2017).","journal-title":"Nat. Methods"},{"key":"2050_CR92","doi-asserted-by":"publisher","first-page":"D613","DOI":"10.1093\/nar\/gkaa1024","volume":"49","author":"M Martens","year":"2021","unstructured":"Martens, M. et al. WikiPathways: connecting communities. Nucleic Acids Res. 49, D613\u2013D621 (2021).","journal-title":"Nucleic Acids Res."},{"key":"2050_CR93","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"2050_CR94","first-page":"D498","volume":"48","author":"B Jassal","year":"2020","unstructured":"Jassal, B. et al. The reactome pathway knowledgebase. Nucleic Acids Res. 48, D498\u2013D503 (2020).","journal-title":"Nucleic Acids Res."},{"key":"2050_CR95","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/1471-2105-15-155","volume":"15","author":"RP Huntley","year":"2014","unstructured":"Huntley, R. P. et al. A method for increasing expressivity of Gene Ontology annotations using a compositional approach. BMC Bioinformatics 15, 155 (2014).","journal-title":"BMC Bioinformatics"},{"key":"2050_CR96","doi-asserted-by":"publisher","first-page":"D833","DOI":"10.1093\/nar\/gkw943","volume":"45","author":"J Pinero","year":"2017","unstructured":"Pinero, J. et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 45, D833\u2013D839 (2017).","journal-title":"Nucleic Acids Res."},{"key":"2050_CR97","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","volume":"32","author":"C Trapnell","year":"2014","unstructured":"Trapnell, C. et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32, 381\u2013386 (2014).","journal-title":"Nat. Biotechnol."},{"key":"2050_CR98","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22801-0","volume":"12","author":"F Wu","year":"2021","unstructured":"Wu, F. et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer. Nat. Commun. 12, 2540 (2021).","journal-title":"Nat. Commun."},{"key":"2050_CR99","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48700-8","volume":"15","author":"M De Zuani","year":"2024","unstructured":"De Zuani, M. et al. Single-cell and spatial transcriptomics analysis of non-small cell lung cancer. Nat. Commun. 15, 4388 (2024).","journal-title":"Nat. Commun."},{"key":"2050_CR100","unstructured":"Ping, J. A single-cell transcriptomic atlas reveals senescence and inflammation in the post-tuberculosis human lung. GitHub https:\/\/github.com\/PINGjl\/Tuberculosis (2024)."}],"container-title":["Nature Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02050-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02050-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02050-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T01:56:25Z","timestamp":1757210185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02050-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":100,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["2050"],"URL":"https:\/\/doi.org\/10.1038\/s41564-025-02050-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2752256\/v1","asserted-by":"object"}]},"ISSN":["2058-5276"],"issn-type":[{"value":"2058-5276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]},"assertion":[{"value":"18 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2025","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"}}]}}