{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:31:47Z","timestamp":1792690307551,"version":"4.5.0"},"reference-count":139,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008868","name":"International Society for Heart and Lung Transplantation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23HL166960"],"award-info":[{"award-number":["K23HL166960"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Cardiovasc Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Allograft rejection following solid-organ transplantation is a major cause of graft dysfunction and mortality. Current diagnostic approaches rely on histology, which exhibits wide diagnostic variability and lacks clinically relevant molecular phenotyping. Here we leverage image-based spatial transcriptomics at subcellular resolution in longitudinal human cardiac biopsies to characterize transcriptional heterogeneity in 62 adult and pediatric heart transplant recipients during and following histologically diagnosed rejection. Across 28 cell types, we identified significant differences in abundance in immune and parenchymal cells across different classes of rejection. We observed broad overlap in transcriptional states across rejection severity and significant heterogeneity within rejection grades. Responders and nonresponders to augmented therapies had distinct transcriptomic profiles, with nonresponders exhibiting baseline T cell hyperactivation and tissue remodeling genes. We also identified cell-specific genes linked to long-term outcomes after heart transplant. These results underscore the importance of subtyping cellular states during rejection to stratify immune\u2013cardiac interactions relevant to short- and long-term outcomes.<\/jats:p>","DOI":"10.1038\/s44161-026-00849-9","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:02:26Z","timestamp":1786352546000},"page":"819-834","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dynamic cellular programs of human cardiac allograft rejection revealed by spatial transcriptomics"],"prefix":"10.1038","volume":"5","author":[{"given":"Kaushik","family":"Amancherla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4408-7211","authenticated-orcid":false,"given":"Angela M. Taravella","family":"Oill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6091-9372","authenticated-orcid":false,"given":"Xavier","family":"Bledsoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2725-0221","authenticated-orcid":false,"given":"Arianna L.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8160-8455","authenticated-orcid":false,"given":"Nelson","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Farrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8951-9295","authenticated-orcid":false,"given":"Quanhu","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1325-4814","authenticated-orcid":false,"given":"David W.","family":"Bearl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5699-9501","authenticated-orcid":false,"given":"Alexander N.","family":"Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan N.","family":"Menachem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan K.","family":"Siddiqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9511-7767","authenticated-orcid":false,"given":"Douglas M.","family":"Brinkley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan D.","family":"Mee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niran","family":"Hadad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9437-5871","authenticated-orcid":false,"given":"Jeffrey","family":"Schmeckpepper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniket","family":"Rali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3566-9799","authenticated-orcid":false,"given":"Stacy","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-3796","authenticated-orcid":false,"given":"Eric","family":"Farber-Eger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4141-1520","authenticated-orcid":false,"given":"Quinn S.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan R.","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Spraggins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly H.","family":"Schlendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4204-8734","authenticated-orcid":false,"given":"Eric R.","family":"Gamazon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2604-3247","authenticated-orcid":false,"given":"Nicholas","family":"Banovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-7156","authenticated-orcid":false,"given":"Ravi V.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"849_CR1","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/ajt.15676","volume":"20","author":"M Colvin","year":"2020","unstructured":"Colvin, M. et al. OPTN\/SRTR 2018 annual data report: heart. Am. J. Transplant. 20, 340\u2013426 (2020).","journal-title":"Am. J. Transplant."},{"key":"849_CR2","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1111\/ajt.15675","volume":"20","author":"JM Smith","year":"2020","unstructured":"Smith, J. M. et al. OPTN\/SRTR 2018 annual data report: intestine. Am. J. Transplant. 20, 300\u2013339 (2020).","journal-title":"Am. J. Transplant."},{"key":"849_CR3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/ajt.15672","volume":"20","author":"A Hart","year":"2020","unstructured":"Hart, A. et al. OPTN\/SRTR 2018 annual data report: kidney. Am. J. Transplant. 20, 20\u2013130 (2020).","journal-title":"Am. J. Transplant."},{"key":"849_CR4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/ajt.15674","volume":"20","author":"A Kwong","year":"2020","unstructured":"Kwong, A. et al. OPTN\/SRTR 2018 annual data report: liver. Am. J. Transplant. 20, 193\u2013299 (2020).","journal-title":"Am. J. Transplant."},{"key":"849_CR5","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1111\/ajt.15673","volume":"20","author":"R Kandaswamy","year":"2020","unstructured":"Kandaswamy, R. et al. OPTN\/SRTR 2018 annual data report: pancreas. Am. J. Transplant. 20, 131\u2013192 (2020).","journal-title":"Am. J. Transplant."},{"key":"849_CR6","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/j.healun.2019.08.004","volume":"38","author":"KK Khush","year":"2019","unstructured":"Khush, K. K. et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult heart transplantation report \u2013 2019; focus theme: donor and recipient size match. J. Heart Lung Transplant. 38, 1056\u20131066 (2019).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR7","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1016\/j.healun.2005.03.019","volume":"24","author":"S Stewart","year":"2005","unstructured":"Stewart, S. et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J. Heart Lung Transplant. 24, 1710\u20131720 (2005).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR8","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/j.healun.2013.08.011","volume":"32","author":"GJ Berry","year":"2013","unstructured":"Berry, G. J. et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J. Heart Lung Transplant. 32, 1147\u20131162 (2013).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR9","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1097\/TP.0b013e31826e19e2","volume":"94","author":"MG Crespo-Leiro","year":"2012","unstructured":"Crespo-Leiro, M. G. et al. Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO II). Transplantation 94, 1172\u20131177 (2012).","journal-title":"Transplantation"},{"key":"849_CR10","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1161\/CIR.0000000000000093","volume":"131","author":"MM Colvin","year":"2015","unstructured":"Colvin, M. M. et al. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation 131, 1608\u20131639 (2015).","journal-title":"Circulation"},{"key":"849_CR11","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.1161\/01.CIR.0000149745.83186.89","volume":"110","author":"J Lindenfeld","year":"2004","unstructured":"Lindenfeld, J. et al. Drug therapy in the heart transplant recipient: part I: cardiac rejection and immunosuppressive drugs. Circulation 110, 3734\u20133740 (2004).","journal-title":"Circulation"},{"key":"849_CR12","doi-asserted-by":"publisher","first-page":"3858","DOI":"10.1161\/01.CIR.0000150332.42276.69","volume":"110","author":"J Lindenfeld","year":"2004","unstructured":"Lindenfeld, J. et al. Drug therapy in the heart transplant recipient: part II: immunosuppressive drugs. Circulation 110, 3858\u20133865 (2004).","journal-title":"Circulation"},{"key":"849_CR13","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.healun.2010.05.017","volume":"29","author":"MR Mehra","year":"2010","unstructured":"Mehra, M. R. et al. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010. J. Heart Lung Transplant. 29, 717\u2013727 (2010).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR14","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1161\/CIRCULATIONAHA.119.044924","volume":"141","author":"A Loupy","year":"2020","unstructured":"Loupy, A. et al. Identification and characterization of trajectories of cardiac allograft vasculopathy after heart transplantation: a population-based study. Circulation 141, 1954\u20131967 (2020).","journal-title":"Circulation"},{"key":"849_CR15","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1002\/ejhf.886","volume":"20","author":"A Lopez-Sainz","year":"2018","unstructured":"Lopez-Sainz, A. et al. Late graft failure in heart transplant recipients: incidence, risk factors and clinical outcomes. Eur. J. Heart Fail. 20, 385\u2013394 (2018).","journal-title":"Eur. J. Heart Fail."},{"key":"849_CR16","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1136\/pgmj.51.595.286","volume":"51","author":"P Caves","year":"1975","unstructured":"Caves, P., Coltart, J., Billingham, M., Rider, A. & Stinson, E. Transvenous endomyocardial biopsy\u2014application of a method for diagnosing heart disease. Postgrad. Med. J. 51, 286\u2013290 (1975).","journal-title":"Postgrad. Med. J."},{"key":"849_CR17","first-page":"e895","volume":"145","author":"PA Heidenreich","year":"2022","unstructured":"Heidenreich, P. A. et al. 2022 AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145, e895\u2013e1032 (2022).","journal-title":"Circulation"},{"key":"849_CR18","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.healun.2009.04.035","volume":"28","author":"AG Kfoury","year":"2009","unstructured":"Kfoury, A. G. et al. Cardiovascular mortality among heart transplant recipients with asymptomatic antibody-mediated or stable mixed cellular and antibody-mediated rejection. J. Heart Lung Transplant. 28, 781\u2013784 (2009).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR19","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/S1010-7940(96)80319-8","volume":"10","author":"B Hausen","year":"1996","unstructured":"Hausen, B. et al. Treatment of recurrent rejection in heart transplantation: cytolytic therapy or bolus steroids?. Eur. J. Cardiothorac. Surg. 10, 905\u2013910 (1996).","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"849_CR20","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1016\/j.jacc.2024.08.010","volume":"84","author":"S Amdani","year":"2024","unstructured":"Amdani, S. et al. Prevalence and impact of recurrent rejection on pediatric heart transplant recipients: a PHTS multi-institutional analysis. J. Am. Coll. Cardiol. 84, 2170\u20132182 (2024).","journal-title":"J. Am. Coll. Cardiol."},{"key":"849_CR21","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41586-022-04817-8","volume":"608","author":"M Chaffin","year":"2022","unstructured":"Chaffin, M. et al. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy. Nature 608, 174\u2013180 (2022).","journal-title":"Nature"},{"key":"849_CR22","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.yjmcc.2024.07.010","volume":"196","author":"R Li","year":"2024","unstructured":"Li, R. et al. Macrophages in the infarcted heart acquire a fibrogenic phenotype, expressing matricellular proteins, but do not undergo fibroblast conversion. J. Mol. Cell. Cardiol. 196, 152\u2013167 (2024).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"849_CR23","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1016\/j.jacc.2011.11.036","volume":"59","author":"M Pichler","year":"2012","unstructured":"Pichler, M., Rainer, P. P., Schauer, S. & Hoefler, G. Cardiac fibrosis in human transplanted hearts is mainly driven by cells of intracardiac origin. J. Am. Coll. Cardiol. 59, 1008\u20131016 (2012).","journal-title":"J. Am. Coll. Cardiol."},{"key":"849_CR24","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.119.009060","volume":"12","author":"A Hughes","year":"2019","unstructured":"Hughes, A. et al. Myocardial fibrosis and prognosis in heart transplant recipients. Circ. Cardiovasc. Imaging 12, e009060 (2019).","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"849_CR25","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1126\/science.abq3061","volume":"381","author":"M Hulsmans","year":"2023","unstructured":"Hulsmans, M. et al. Recruited macrophages elicit atrial fibrillation. Science 381, 231\u2013239 (2023).","journal-title":"Science"},{"key":"849_CR26","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.001461","volume":"1","author":"A Thajudeen","year":"2012","unstructured":"Thajudeen, A. et al. Arrhythmias after heart transplantation: mechanisms and management. J. Am. Heart Assoc. 1, e001461 (2012).","journal-title":"J. Am. Heart Assoc."},{"key":"849_CR27","volume":"14","author":"JA Joglar","year":"2021","unstructured":"Joglar, J. A. et al. Management of arrhythmias after heart transplant: current state and considerations for future research. Circulation 14, e007954 (2021).","journal-title":"Circulation"},{"key":"849_CR28","volume":"16","author":"K Amancherla","year":"2023","unstructured":"Amancherla, K. et al. Single-nuclear RNA sequencing of endomyocardial biopsies identifies persistence of donor-recipient chimerism with distinct signatures in severe cardiac allograft vasculopathy. Circulation 16, e010119 (2023).","journal-title":"Circulation"},{"key":"849_CR29","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0092-8674(00)80059-8","volume":"99","author":"R Forster","year":"1999","unstructured":"Forster, R. et al. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99, 23\u201333 (1999).","journal-title":"Cell"},{"key":"849_CR30","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1111\/j.1600-6143.2004.00453.x","volume":"4","author":"AW Bingaman","year":"2004","unstructured":"Bingaman, A. W. & Farber, D. L. Memory T cells in transplantation: generation, function, and potential role in rejection. Am. J. Transplant. 4, 846\u2013852 (2004).","journal-title":"Am. J. Transplant."},{"key":"849_CR31","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1161\/hc4601.098010","volume":"104","author":"M Melter","year":"2001","unstructured":"Melter, M. et al. Expression of the chemokine receptor CXCR3 and its ligand IP-10 during human cardiac allograft rejection. Circulation 104, 2558\u20132564 (2001).","journal-title":"Circulation"},{"key":"849_CR32","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1084\/jem.192.10.1515","volume":"192","author":"WW Hancock","year":"2000","unstructured":"Hancock, W. W. et al. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J. Exp. Med. 192, 1515\u20131520 (2000).","journal-title":"J. Exp. Med."},{"key":"849_CR33","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.healun.2022.10.017","volume":"42","author":"D Kong","year":"2023","unstructured":"Kong, D. et al. The dynamic cellular landscape of grafts with acute rejection after heart transplantation. J. Heart Lung Transplant. 42, 160\u2013172 (2023).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR34","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1111\/j.1600-6143.2010.03089.x","volume":"10","author":"K Yamaura","year":"2010","unstructured":"Yamaura, K. et al. Differential requirement of CD27 costimulatory signaling for naive versus alloantigen-primed effector\/memory CD8+ T cells. Am. J. Transplant. 10, 1210\u20131220 (2010).","journal-title":"Am. J. Transplant."},{"key":"849_CR35","doi-asserted-by":"publisher","first-page":"S36","DOI":"10.1097\/00007890-200201151-00012","volume":"73","author":"A Yamada And","year":"2002","unstructured":"Yamada And, A. & Sayegh, M. H. The CD154\u2013CD40 costimulatory pathway in transplantation. Transplantation 73, S36\u2013S39 (2002).","journal-title":"Transplantation"},{"key":"849_CR36","doi-asserted-by":"publisher","first-page":"399","DOI":"10.2217\/imt.15.1","volume":"7","author":"DF Pinelli","year":"2015","unstructured":"Pinelli, D. F. & Ford, M. L. Novel insights into anti-CD40\/CD154 immunotherapy in transplant tolerance. Immunotherapy 7, 399\u2013410 (2015).","journal-title":"Immunotherapy"},{"key":"849_CR37","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1182\/blood.V99.3.957","volume":"99","author":"D Howie","year":"2002","unstructured":"Howie, D. et al. Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150\/SAP binding and CD150-mediated costimulation. Blood 99, 957\u2013965 (2002).","journal-title":"Blood"},{"key":"849_CR38","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo0686","volume":"14","author":"AH Jonsson","year":"2022","unstructured":"Jonsson, A. H. et al. Granzyme K+ CD8 T cells form a core population in inflamed human tissue. Sci. Transl. Med. 14, eabo0686 (2022).","journal-title":"Sci. Transl. Med."},{"key":"849_CR39","doi-asserted-by":"publisher","first-page":"5530","DOI":"10.4049\/jimmunol.168.11.5530","volume":"168","author":"C Chirathaworn","year":"2002","unstructured":"Chirathaworn, C. et al. Stimulation through intercellular adhesion molecule-1 provides a second signal for T cell activation. J. Immunol. 168, 5530\u20135537 (2002).","journal-title":"J. Immunol."},{"key":"849_CR40","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/sj.onc.1206126","volume":"22","author":"S Baumann","year":"2003","unstructured":"Baumann, S. et al. An unexpected role for FosB in activation-induced cell death of T cells. Oncogene 22, 1333\u20131339 (2003).","journal-title":"Oncogene"},{"key":"849_CR41","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","volume":"571","author":"O Khan","year":"2019","unstructured":"Khan, O. et al. TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature 571, 211\u2013218 (2019).","journal-title":"Nature"},{"key":"849_CR42","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1038\/s41590-023-01569-z","volume":"24","author":"V Aggarwal","year":"2023","unstructured":"Aggarwal, V., Workman, C. J. & Vignali, D. A. A. LAG-3 as the third checkpoint inhibitor. Nat. Immunol. 24, 1415\u20131422 (2023).","journal-title":"Nat. Immunol."},{"key":"849_CR43","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1126\/science.7542801","volume":"269","author":"A Tarakhovsky","year":"1995","unstructured":"Tarakhovsky, A. et al. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 269, 535\u2013537 (1995).","journal-title":"Science"},{"key":"849_CR44","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1038\/ni.3540","volume":"17","author":"T Chinen","year":"2016","unstructured":"Chinen, T. et al. An essential role for the IL-2 receptor in Treg cell function. Nat. Immunol. 17, 1322\u20131333 (2016).","journal-title":"Nat. Immunol."},{"key":"849_CR45","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/S0165-5728(00)00435-5","volume":"113","author":"KI Omari","year":"2001","unstructured":"Omari, K. I. & Dorovini-Zis, K. Expression and function of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in an in vitro model of the human blood\u2013brain barrier. J. Neuroimmunol. 113, 129\u2013141 (2001).","journal-title":"J. Neuroimmunol."},{"key":"849_CR46","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1182\/blood-2012-07-442541","volume":"121","author":"DA Mancardi","year":"2013","unstructured":"Mancardi, D. A. et al. The high-affinity human IgG receptor FcgammaRI (CD64) promotes IgG-mediated inflammation, anaphylaxis, and antitumor immunotherapy. Blood 121, 1563\u20131573 (2013).","journal-title":"Blood"},{"key":"849_CR47","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1056\/NEJMoa1100066","volume":"365","author":"S Hambleton","year":"2011","unstructured":"Hambleton, S. et al. IRF8 mutations and human dendritic-cell immunodeficiency. N. Engl. J. Med. 365, 127\u2013138 (2011).","journal-title":"N. Engl. J. Med."},{"key":"849_CR48","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.coi.2012.11.004","volume":"25","author":"M Basler","year":"2013","unstructured":"Basler, M., Kirk, C. J. & Groettrup, M. The immunoproteasome in antigen processing and other immunological functions. Curr. Opin. Immunol. 25, 74\u201380 (2013).","journal-title":"Curr. Opin. Immunol."},{"key":"849_CR49","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.ccell.2020.03.016","volume":"37","author":"E Dheilly","year":"2020","unstructured":"Dheilly, E. et al. Cathepsin S regulates antigen processing and T cell activity in non-Hodgkin lymphoma. Cancer Cell 37, 674\u2013689 (2020).","journal-title":"Cancer Cell"},{"key":"849_CR50","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1002\/eji.200425949","volume":"35","author":"BA Bladergroen","year":"2005","unstructured":"Bladergroen, B. A. et al. The granzyme B inhibitor proteinase inhibitor 9 (PI9) is expressed by human mast cells. Eur. J. Immunol. 35, 1175\u20131183 (2005).","journal-title":"Eur. J. Immunol."},{"key":"849_CR51","doi-asserted-by":"publisher","first-page":"4605","DOI":"10.4049\/jimmunol.177.7.4605","volume":"177","author":"K Takahashi","year":"2006","unstructured":"Takahashi, K., Hayashi, N., Kaminogawa, S. & Ra, C. Molecular mechanisms for transcriptional regulation of human high-affinity IgE receptor beta-chain gene induced by GM-CSF. J. Immunol. 177, 4605\u20134611 (2006).","journal-title":"J. Immunol."},{"key":"849_CR52","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0952-3278(03)00077-2","volume":"69","author":"Y Kanaoka","year":"2003","unstructured":"Kanaoka, Y. & Urade, Y. Hematopoietic prostaglandin D synthase. Prostaglandins Leukot. Essent. Fatty Acids 69, 163\u2013167 (2003).","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"849_CR53","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1161\/CIRCRESAHA.116.306853","volume":"118","author":"JH Foley","year":"2016","unstructured":"Foley, J. H. & Conway, E. M. Cross talk pathways between coagulation and inflammation. Circ. Res. 118, 1392\u20131408 (2016).","journal-title":"Circ. Res."},{"key":"849_CR54","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1194\/jlr.M600489-JLR200","volume":"48","author":"CD Anfuso","year":"2007","unstructured":"Anfuso, C. D. et al. Endothelial cell\u2013pericyte cocultures induce PLA2 protein expression through activation of PKCalpha and the MAPK\/ERK cascade. J. Lipid Res. 48, 782\u2013793 (2007).","journal-title":"J. Lipid Res."},{"key":"849_CR55","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.healun.2021.08.004","volume":"41","author":"PF Halloran","year":"2022","unstructured":"Halloran, P. F. et al. Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes. J. Heart Lung Transplant. 41, 334\u2013344 (2022).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR56","doi-asserted-by":"publisher","first-page":"12123","DOI":"10.1073\/pnas.1201453109","volume":"109","author":"F Miyagawa","year":"2012","unstructured":"Miyagawa, F. et al. Interferon regulatory factor 8 integrates T-cell receptor and cytokine-signaling pathways and drives effector differentiation of CD8 T cells. Proc. Natl Acad. Sci. USA 109, 12123\u201312128 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"849_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29173-z","volume":"13","author":"J Huuhtanen","year":"2022","unstructured":"Huuhtanen, J. et al. Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8+ T-cell large granular lymphocytic leukemia. Nat. Commun. 13, 1981 (2022).","journal-title":"Nat. Commun."},{"key":"849_CR58","doi-asserted-by":"publisher","unstructured":"Kwon, R. et al. Regulation of tumor growth by leukocyte-specific protein 1 in T cells. J. Immunother. Cancer https:\/\/doi.org\/10.1136\/jitc-2020-001180 (2020).","DOI":"10.1136\/jitc-2020-001180"},{"key":"849_CR59","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1161\/CIRCRESAHA.120.318124","volume":"128","author":"JP Monteiro","year":"2021","unstructured":"Monteiro, J. P. et al. MIR503HG loss promotes endothelial-to-mesenchymal transition in vascular disease. Circ. Res. 128, 1173\u20131190 (2021).","journal-title":"Circ. Res."},{"key":"849_CR60","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1126\/science.7688481","volume":"261","author":"PE Love","year":"1993","unstructured":"Love, P. E. et al. T cell development in mice that lack the zeta chain of the T cell antigen receptor complex. Science 261, 918\u2013921 (1993).","journal-title":"Science"},{"key":"849_CR61","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1146\/annurev.immunol.23.021704.115625","volume":"23","author":"ME Call","year":"2005","unstructured":"Call, M. E. & Wucherpfennig, K. W. The T cell receptor: critical role of the membrane environment in receptor assembly and function. Annu. Rev. Immunol. 23, 101\u2013125 (2005).","journal-title":"Annu. Rev. Immunol."},{"key":"849_CR62","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.immuni.2016.04.020","volume":"44","author":"JH Esensten","year":"2016","unstructured":"Esensten, J. H., Helou, Y. A., Chopra, G., Weiss, A. & Bluestone, J. A. CD28 costimulation: from mechanism to therapy. Immunity 44, 973\u2013988 (2016).","journal-title":"Immunity"},{"key":"849_CR63","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/eji.201646837","volume":"47","author":"D Cibrian","year":"2017","unstructured":"Cibrian, D. & Sanchez-Madrid, F. CD69: from activation marker to metabolic gatekeeper. Eur. J. Immunol. 47, 946\u2013953 (2017).","journal-title":"Eur. J. Immunol."},{"key":"849_CR64","doi-asserted-by":"publisher","first-page":"6571","DOI":"10.4049\/jimmunol.174.11.6571","volume":"174","author":"TJ Fry","year":"2005","unstructured":"Fry, T. J. & Mackall, C. L. The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J. Immunol. 174, 6571\u20136576 (2005).","journal-title":"J. Immunol."},{"key":"849_CR65","doi-asserted-by":"publisher","first-page":"428","DOI":"10.4049\/jimmunol.1201361","volume":"190","author":"TS Tai","year":"2013","unstructured":"Tai, T. S., Pai, S. Y. & Ho, I. C. GATA-3 regulates the homeostasis and activation of CD8+ T cells. J. Immunol. 190, 428\u2013437 (2013).","journal-title":"J. Immunol."},{"key":"849_CR66","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/nri2476","volume":"9","author":"IC Ho","year":"2009","unstructured":"Ho, I. C., Tai, T. S. & Pai, S. Y. GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat. Rev. Immunol. 9, 125\u2013135 (2009).","journal-title":"Nat. Rev. Immunol."},{"key":"849_CR67","doi-asserted-by":"publisher","first-page":"13","DOI":"10.12703\/P6-13","volume":"6","author":"FO Martinez","year":"2014","unstructured":"Martinez, F. O. & Gordon, S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 6, 13 (2014).","journal-title":"F1000Prime Rep."},{"key":"849_CR68","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.matbio.2022.04.005","volume":"110","author":"C Huang","year":"2022","unstructured":"Huang, C. et al. Asporin, an extracellular matrix protein, is a beneficial regulator of cardiac remodeling. Matrix Biol. 110, 40\u201359 (2022).","journal-title":"Matrix Biol."},{"key":"849_CR69","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/S0002-9440(10)63975-2","volume":"158","author":"L Nelimarkka","year":"2001","unstructured":"Nelimarkka, L. et al. Decorin is produced by capillary endothelial cells in inflammation-associated angiogenesis. Am. J. Pathol. 158, 345\u2013353 (2001).","journal-title":"Am. J. Pathol."},{"key":"849_CR70","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.717962","volume":"8","author":"Y Xue","year":"2021","unstructured":"Xue, Y. et al. STAT3 and IL-6 contribute to corticosteroid resistance in an OVA and ozone-induced asthma model with neutrophil infiltration. Front. Mol. Biosci. 8, 717962 (2021).","journal-title":"Front. Mol. Biosci."},{"key":"849_CR71","doi-asserted-by":"publisher","first-page":"12942","DOI":"10.1073\/pnas.1821565116","volume":"116","author":"K Dendoncker","year":"2019","unstructured":"Dendoncker, K. et al. TNF-alpha inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile. Proc. Natl Acad. Sci. USA 116, 12942\u201312951 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"849_CR72","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1002\/hep.24655","volume":"55","author":"A Dittrich","year":"2012","unstructured":"Dittrich, A. et al. Glucocorticoids increase interleukin-6-dependent gene induction by interfering with the expression of the suppressor of cytokine signaling 3 feedback inhibitor. Hepatology 55, 256\u2013266 (2012).","journal-title":"Hepatology"},{"key":"849_CR73","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85408-x","volume":"11","author":"DM Favara","year":"2021","unstructured":"Favara, D. M. et al. Elevated expression of the adhesion GPCR ADGRL4\/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling. Sci. Rep. 11, 8870 (2021).","journal-title":"Sci. Rep."},{"key":"849_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15867-8","volume":"7","author":"J Zhao","year":"2017","unstructured":"Zhao, J. et al. Chemokines protect vascular smooth muscle cells from cell death induced by cyclic mechanical stretch. Sci. Rep. 7, 16128 (2017).","journal-title":"Sci. Rep."},{"key":"849_CR75","doi-asserted-by":"publisher","first-page":"5693","DOI":"10.4049\/jimmunol.172.9.5693","volume":"172","author":"A Ghanekar","year":"2004","unstructured":"Ghanekar, A. et al. Endothelial induction of fgl2 contributes to thrombosis during acute vascular xenograft rejection. J. Immunol. 172, 5693\u20135701 (2004).","journal-title":"J. Immunol."},{"key":"849_CR76","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1002\/jcp.24870","volume":"230","author":"Z Xu","year":"2015","unstructured":"Xu, Z. et al. Transcription factor MEF2C suppresses endothelial cell inflammation via regulation of NF-kappaB and KLF2. J. Cell. Physiol. 230, 1310\u20131320 (2015).","journal-title":"J. Cell. Physiol."},{"key":"849_CR77","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1161\/ATVBAHA.112.254664","volume":"32","author":"G Litteri","year":"2012","unstructured":"Litteri, G. et al. Vascular smooth muscle Emilin-1 is a regulator of arteriolar myogenic response and blood pressure. Arterioscler. Thromb. Vasc. Biol. 32, 2178\u20132184 (2012).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"849_CR78","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1111\/jth.15171","volume":"19","author":"A Leatherdale","year":"2021","unstructured":"Leatherdale, A. et al. Multimerin 1 supports platelet function in vivo and binds to specific GPAGPOGPX motifs in fibrillar collagens that enhance platelet adhesion. J. Thromb. Haemost. 19, 547\u2013561 (2021).","journal-title":"J. Thromb. Haemost."},{"key":"849_CR79","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1161\/CIRCULATIONAHA.116.022907","volume":"135","author":"A Loupy","year":"2017","unstructured":"Loupy, A. et al. Gene expression profiling for the identification and classification of antibody-mediated heart rejection. Circulation 135, 917\u2013935 (2017).","journal-title":"Circulation"},{"key":"849_CR80","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1172\/JCI11871","volume":"107","author":"MI Cybulsky","year":"2001","unstructured":"Cybulsky, M. I. et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J. Clin. Invest. 107, 1255\u20131262 (2001).","journal-title":"J. Clin. Invest."},{"key":"849_CR81","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.2353\/ajpath.2006.050473","volume":"168","author":"D Rosner","year":"2006","unstructured":"Rosner, D. et al. Interferon-gamma induces Fas trafficking and sensitization to apoptosis in vascular smooth muscle cells via a PI3K- and Akt-dependent mechanism. Am. J. Pathol. 168, 2054\u20132063 (2006).","journal-title":"Am. J. Pathol."},{"key":"849_CR82","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1161\/01.RES.86.10.1038","volume":"86","author":"SW Chan","year":"2000","unstructured":"Chan, S. W. et al. Sensitivity to Fas-mediated apoptosis is determined below receptor level in human vascular smooth muscle cells. Circ. Res. 86, 1038\u20131046 (2000).","journal-title":"Circ. Res."},{"key":"849_CR83","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1161\/01.ATV.20.2.309","volume":"20","author":"M Sata","year":"2000","unstructured":"Sata, M., Suhara, T. & Walsh, K. Vascular endothelial cells and smooth muscle cells differ in expression of Fas and Fas ligand and in sensitivity to Fas ligand-induced cell death: implications for vascular disease and therapy. Arterioscler. Thromb. Vasc. Biol. 20, 309\u2013316 (2000).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"849_CR84","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1055\/s-0037-1615114","volume":"79","author":"L Zhou","year":"1998","unstructured":"Zhou, L. et al. CD40 engagement on endothelial cells promotes tissue factor-dependent procoagulant activity. Thromb. Haemost. 79, 1025\u20131028 (1998).","journal-title":"Thromb. Haemost."},{"key":"849_CR85","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.healun.2022.01.1377","volume":"41","author":"BD Piening","year":"2022","unstructured":"Piening, B. D. et al. Whole transcriptome profiling of prospective endomyocardial biopsies reveals prognostic and diagnostic signatures of cardiac allograft rejection. J. Heart Lung Transplant. 41, 840\u2013848 (2022).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR86","doi-asserted-by":"publisher","first-page":"4570","DOI":"10.1038\/s44319-024-00251-1","volume":"25","author":"AT Stock","year":"2024","unstructured":"Stock, A. T. et al. mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis. EMBO Rep. 25, 4570\u20134593 (2024).","journal-title":"EMBO Rep."},{"key":"849_CR87","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07858-8","volume":"10","author":"HV Woodcock","year":"2019","unstructured":"Woodcock, H. V. et al. The mTORC1\/4E-BP1 axis represents a critical signaling node during fibrogenesis. Nat. Commun. 10, 6 (2019).","journal-title":"Nat. Commun."},{"key":"849_CR88","doi-asserted-by":"publisher","unstructured":"Plate, M., Guillotin, D. & Chambers, R. C. The promise of mTOR as a therapeutic target pathway in idiopathic pulmonary fibrosis. Eur. Respir. Rev. https:\/\/doi.org\/10.1183\/16000617.0269-2020 (2020).","DOI":"10.1183\/16000617.0269-2020"},{"key":"849_CR89","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1161\/01.CIR.0000027822.23269.07","volume":"106","author":"T Wang","year":"2002","unstructured":"Wang, T. et al. Overexpression of soluble fas attenuates transplant arteriosclerosis in rat aortic allografts. Circulation 106, 1536\u20131542 (2002).","journal-title":"Circulation"},{"key":"849_CR90","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1161\/ATVBAHA.107.151456","volume":"27","author":"A Woodfin","year":"2007","unstructured":"Woodfin, A., Voisin, M. B. & Nourshargh, S. PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arterioscler. Thromb. Vasc. Biol. 27, 2514\u20132523 (2007).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"849_CR91","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s00018-023-04883-9","volume":"80","author":"Y Zhou","year":"2023","unstructured":"Zhou, Y. et al. SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin. Cell. Mol. Life Sci. 80, 264 (2023).","journal-title":"Cell. Mol. Life Sci."},{"key":"849_CR92","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1161\/CIRCULATIONAHA.123.064155","volume":"148","author":"L Alex","year":"2023","unstructured":"Alex, L. et al. Cardiac pericytes acquire a fibrogenic phenotype and contribute to vascular maturation after myocardial infarction. Circulation 148, 882\u2013898 (2023).","journal-title":"Circulation"},{"key":"849_CR93","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.599415","volume":"11","author":"V Sorokin","year":"2020","unstructured":"Sorokin, V. et al. Role of vascular smooth muscle cell plasticity and interactions in vessel wall inflammation. Front. Immunol. 11, 599415 (2020).","journal-title":"Front. Immunol."},{"key":"849_CR94","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1161\/01.RES.88.1.37","volume":"88","author":"TE Bunton","year":"2001","unstructured":"Bunton, T. E. et al. Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome. Circ. Res. 88, 37\u201343 (2001).","journal-title":"Circ. Res."},{"key":"849_CR95","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018062","volume":"10","author":"W Wang","year":"2021","unstructured":"Wang, W. et al. LINC01278 sponges miR-500b-5p to regulate the expression of ACTG2 to control phenotypic switching in human vascular smooth muscle cells during aortic dissection. J. Am. Heart Assoc. 10, e018062 (2021).","journal-title":"J. Am. Heart Assoc."},{"key":"849_CR96","doi-asserted-by":"publisher","unstructured":"Wang, Z., Zhuang, X., Chen, B. & Wei, M. Osteoglycin knockdown promotes vascular smooth muscle cell proliferation and migration in aortic dissection via the VEGF\/VEGFR2 axis. Mol. Med. Rep. https:\/\/doi.org\/10.3892\/mmr.2020.11703 (2021).","DOI":"10.3892\/mmr.2020.11703"},{"key":"849_CR97","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.immuni.2016.08.013","volume":"45","author":"D Sichien","year":"2016","unstructured":"Sichien, D. et al. IRF8 transcription factor controls survival and function of terminally differentiated conventional and plasmacytoid dendritic cells, respectively. Immunity 45, 626\u2013640 (2016).","journal-title":"Immunity"},{"key":"849_CR98","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112864","volume":"42","author":"A Sapoznikov","year":"2023","unstructured":"Sapoznikov, A. et al. Dendritic cell ICAM-1 strengthens synapses with CD8 T cells but is not required for their early differentiation. Cell Rep. 42, 112864 (2023).","journal-title":"Cell Rep."},{"key":"849_CR99","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/JLB.3MR0621-616RR","volume":"111","author":"YD Xu","year":"2022","unstructured":"Xu, Y. D., Cheng, M., Shang, P. P. & Yang, Y. Q. Role of IL-6 in dendritic cell functions. J. Leukoc. Biol. 111, 695\u2013709 (2022).","journal-title":"J. Leukoc. Biol."},{"key":"849_CR100","doi-asserted-by":"publisher","first-page":"5488","DOI":"10.1182\/blood-2008-10-187179","volume":"113","author":"L Chiossone","year":"2009","unstructured":"Chiossone, L. et al. Maturation of mouse NK cells is a 4-stage developmental program. Blood 113, 5488\u20135496 (2009).","journal-title":"Blood"},{"key":"849_CR101","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/eji.202149406","volume":"52","author":"A Gutierrez-Guerrero","year":"2022","unstructured":"Gutierrez-Guerrero, A. et al. SLAMF7 selectively favors degranulation to promote cytotoxicity in human NK cells. Eur. J. Immunol. 52, 62\u201374 (2022).","journal-title":"Eur. J. Immunol."},{"key":"849_CR102","doi-asserted-by":"publisher","unstructured":"Vemuri, K. et al. CD93 maintains endothelial barrier function and limits metastatic dissemination. JCI Insight https:\/\/doi.org\/10.1172\/jci.insight.169830 (2024).","DOI":"10.1172\/jci.insight.169830"},{"key":"849_CR103","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2221742120","volume":"120","author":"F Alonso","year":"2023","unstructured":"Alonso, F. et al. Fibrillin-1 regulates endothelial sprouting during angiogenesis. Proc. Natl Acad. Sci. USA 120, e2221742120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"849_CR104","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1242\/jcs.028241","volume":"122","author":"VR Sobrado","year":"2009","unstructured":"Sobrado, V. R. et al. The class I bHLH factors E2-2A and E2-2B regulate EMT. J. Cell Sci. 122, 1014\u20131024 (2009).","journal-title":"J. Cell Sci."},{"key":"849_CR105","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41586-024-08008-5","volume":"635","author":"JM Amrute","year":"2024","unstructured":"Amrute, J. M. et al. Targeting immune-fibroblast cell communication in heart failure. Nature 635, 423\u2013433 (2024).","journal-title":"Nature"},{"key":"849_CR106","doi-asserted-by":"publisher","unstructured":"Trempus, C. S. et al. Functional Pdgfra fibroblast heterogeneity in normal and fibrotic mouse lung. JCI Insight https:\/\/doi.org\/10.1172\/jci.insight.164380 (2023).","DOI":"10.1172\/jci.insight.164380"},{"key":"849_CR107","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911021","volume":"12","author":"EM Buhl","year":"2020","unstructured":"Buhl, E. M. et al. Dysregulated mesenchymal PDGFR-beta drives kidney fibrosis. EMBO Mol. Med. 12, e11021 (2020).","journal-title":"EMBO Mol. Med."},{"key":"849_CR108","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41571-019-0273-6","volume":"17","author":"JT Yurkovich","year":"2020","unstructured":"Yurkovich, J. T., Tian, Q., Price, N. D. & Hood, L. A systems approach to clinical oncology uses deep phenotyping to deliver personalized care. Nat. Rev. Clin. Oncol. 17, 183\u2013194 (2020).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"849_CR109","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.stem.2022.04.006","volume":"29","author":"S Ding","year":"2022","unstructured":"Ding, S. et al. Patient-derived micro-organospheres enable clinical precision oncology. Cell Stem Cell 29, 905\u2013917 (2022).","journal-title":"Cell Stem Cell"},{"key":"849_CR110","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.annonc.2022.05.522","volume":"33","author":"E Pleasance","year":"2022","unstructured":"Pleasance, E. et al. Whole-genome and transcriptome analysis enhances precision cancer treatment options. Ann. Oncol. 33, 939\u2013949 (2022).","journal-title":"Ann. Oncol."},{"key":"849_CR111","first-page":"102710","volume":"13","author":"S Huang","year":"2025","unstructured":"Huang, S. et al. Cardiovascular\u2013kidney\u2013metabolic disease burden in children and adults following heart transplantation. J. Am. Coll. Cardiol. 13, 102710 (2025).","journal-title":"J. Am. Coll. Cardiol."},{"key":"849_CR112","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1016\/j.cardfail.2025.08.021","volume":"32","author":"S Huang","year":"2026","unstructured":"Huang, S. et al. Antibody-independent microvascular inflammation impacts long-term risk in heart transplantation. J. Card. Fail. 32, 1166\u20131172 (2026).","journal-title":"J. Card. Fail."},{"key":"849_CR113","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1161\/ATVBAHA.114.302818","volume":"34","author":"JS Pober","year":"2014","unstructured":"Pober, J. S., Jane-wit, D., Qin, L. & Tellides, G. Interacting mechanisms in the pathogenesis of cardiac allograft vasculopathy. Arterioscler. Thromb. Vasc. Biol. 34, 1609\u20131614 (2014).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"849_CR114","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/35003221","volume":"403","author":"G Tellides","year":"2000","unstructured":"Tellides, G. et al. Interferon-gamma elicits arteriosclerosis in the absence of leukocytes. Nature 403, 207\u2013211 (2000).","journal-title":"Nature"},{"key":"849_CR115","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12862-019-1445-9","volume":"19","author":"DM Favara","year":"2019","unstructured":"Favara, D. M., Banham, A. H. & Harris, A. L. ADGRL4\/ELTD1 is a highly conserved angiogenesis-associated orphan adhesion GPCR that emerged with the first vertebrates and comprises 3 evolutionary variants. BMC Evol. Biol. 19, 143 (2019).","journal-title":"BMC Evol. Biol."},{"key":"849_CR116","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/ng.2007.47","volume":"40","author":"DS Cunninghame Graham","year":"2008","unstructured":"Cunninghame Graham, D. S. et al. Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nat. Genet. 40, 83\u201389 (2008).","journal-title":"Nat. Genet."},{"key":"849_CR117","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1161\/CIRCULATIONAHA.109.913921","volume":"123","author":"CT Holweg","year":"2011","unstructured":"Holweg, C. T. et al. Identification and classification of acute cardiac rejection by intragraft transcriptional profiling. Circulation 123, 2236\u20132243 (2011).","journal-title":"Circulation"},{"key":"849_CR118","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1471-2261-6-29","volume":"6","author":"K Karason","year":"2006","unstructured":"Karason, K., Jernas, M., Hagg, D. A. & Svensson, P. A. Evaluation of CXCL9 and CXCL10 as circulating biomarkers of human cardiac allograft rejection. BMC Cardiovasc. Disord. 6, 29 (2006).","journal-title":"BMC Cardiovasc. Disord."},{"key":"849_CR119","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.healun.2017.05.029","volume":"36","author":"PF Halloran","year":"2017","unstructured":"Halloran, P. F. et al. Building a tissue-based molecular diagnostic system in heart transplant rejection: the heart Molecular Microscope Diagnostic (MMDx) system. J. Heart Lung Transplant. 36, 1192\u20131200 (2017).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR120","doi-asserted-by":"publisher","unstructured":"Halloran, P. F. et al. Exploring the cardiac response to injury in heart transplant biopsies. JCI Insight https:\/\/doi.org\/10.1172\/jci.insight.123674 (2018).","DOI":"10.1172\/jci.insight.123674"},{"key":"849_CR121","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.healun.2019.01.1318","volume":"38","author":"MD Parkes","year":"2019","unstructured":"Parkes, M. D. et al. An integrated molecular diagnostic report for heart transplant biopsies using an ensemble of diagnostic algorithms. J. Heart Lung Transplant. 38, 636\u2013646 (2019).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR122","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.healun.2023.11.013","volume":"43","author":"PF Halloran","year":"2024","unstructured":"Halloran, P. F. et al. Molecular states associated with dysfunction and graft loss in heart transplants. J. Heart Lung Transplant. 43, 508\u2013518 (2024).","journal-title":"J. Heart Lung Transplant."},{"key":"849_CR123","doi-asserted-by":"publisher","unstructured":"Dann, E. et al. Estimating the impact of single-cell RNA sequencing of human tissues on drug target validation. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2024.04.04.24305313 (2024).","DOI":"10.1101\/2024.04.04.24305313"},{"key":"849_CR124","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41573-023-00688-4","volume":"22","author":"B Van de Sande","year":"2023","unstructured":"Van de Sande, B. et al. Applications of single-cell RNA sequencing in drug discovery and development. Nat. Rev. Drug Discov. 22, 496\u2013520 (2023).","journal-title":"Nat. Rev. Drug Discov."},{"key":"849_CR125","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/s41586-020-2797-4","volume":"588","author":"M Litvinukova","year":"2020","unstructured":"Litvinukova, M. et al. Cells of the adult human heart. Nature 588, 466\u2013472 (2020).","journal-title":"Nature"},{"key":"849_CR126","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo1984","volume":"377","author":"D Reichart","year":"2022","unstructured":"Reichart, D. et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science 377, eabo1984 (2022).","journal-title":"Science"},{"key":"849_CR127","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/s41586-022-05060-x","volume":"608","author":"C Kuppe","year":"2022","unstructured":"Kuppe, C. et al. Spatial multi-omic map of human myocardial infarction. Nature 608, 766\u2013777 (2022).","journal-title":"Nature"},{"key":"849_CR128","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s44161-023-00260-8","volume":"2","author":"JM Amrute","year":"2023","unstructured":"Amrute, J. M. et al. Defining cardiac functional recovery in end-stage heart failure at single-cell resolution. Nat. Cardiovasc. Res. 2, 399\u2013416 (2023).","journal-title":"Nat. Cardiovasc. Res."},{"key":"849_CR129","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293\u2013304 (2024).","journal-title":"Nat. Biotechnol."},{"key":"849_CR130","unstructured":"Posit Team RStudio: Integrated Development Environment for R (Posit Software, 2026); https:\/\/posit.co\/"},{"key":"849_CR131","unstructured":"RAPIDS Development Team RAPIDS: Libraries for End to End GPU Data Science (Version 21.8.1) (RAPIDS, 2021); https:\/\/rapids.ai\/"},{"key":"849_CR132","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0","volume":"19","author":"FA Wolf","year":"2018","unstructured":"Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).","journal-title":"Genome Biol."},{"key":"849_CR133","unstructured":"van Rossum, G. Python v3.10.13 (Python Software Foundation, 2021)."},{"key":"849_CR134","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02080-x","author":"A Vannan","year":"2025","unstructured":"Vannan, A. et al. Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis. Nat. Genet. https:\/\/doi.org\/10.1038\/s41588-025-02080-x (2025).","journal-title":"Nat. Genet."},{"key":"849_CR135","doi-asserted-by":"publisher","unstructured":"Korsunsky, I., Nathan, A., Millard, N. & Raychaudhuri, S. Presto scales Wilcoxon and auROC analyses to millions of observations. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/653253 (2019).","DOI":"10.1101\/653253"},{"key":"849_CR136","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5","volume":"7","author":"P Bankhead","year":"2017","unstructured":"Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).","journal-title":"Sci. Rep."},{"key":"849_CR137","unstructured":"Kassambara, A., Mundt, F. & Erdey, L. factoextra: extract and visualize the results of multivariate data analyses. R version 1.0.7.999 https:\/\/CRAN.R-project.org\/package=factoextra (2020)."},{"key":"849_CR138","doi-asserted-by":"publisher","first-page":"4720","DOI":"10.1093\/bioinformatics\/btac582","volume":"38","author":"B Phipson","year":"2022","unstructured":"Phipson, B. et al. propeller: testing for differences in cell type proportions in single cell data. Bioinformatics 38, 4720\u20134726 (2022).","journal-title":"Bioinformatics"},{"key":"849_CR139","doi-asserted-by":"publisher","first-page":"378","DOI":"10.32614\/RJ-2017-066","volume":"9","author":"ME Brooks","year":"2017","unstructured":"Brooks, M. E. et al. glmmTMB balances speed and flexibility among packages for zero-inflated generalized linear mixed modeling. R J. 9, 378\u2013400 (2017).","journal-title":"R J."}],"container-title":["Nature Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00849-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00849-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00849-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:02:23Z","timestamp":1789074143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00849-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":139,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["849"],"URL":"https:\/\/doi.org\/10.1038\/s44161-026-00849-9","relation":{},"ISSN":["2731-0590"],"issn-type":[{"value":"2731-0590","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"assertion":[{"value":"17 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K.A., N.B. and R.V.S. have institutional disclosures filed for spatial RNA biomarkers of transplant rejection and allograft health. R.V.S. has equity ownership in and is a consultant for Thryv Therapeutics. R.V.S. is a co-inventor on pending patents or disclosures on molecular biomarkers of fitness, lung disease, cardiovascular diseases and phenotypes, and metabolic health, use of RNAs (including spatial) as therapeutics and diagnostic biomarkers in disease, and methods in metabolomics. E.R.G. is a consultant for Thryv Therapeutics and is a co-inventor on pending patents or disclosures on cardiovascular diseases and phenotypes, and metabolic health, use of RNAs as therapeutics and diagnostic biomarkers in disease, and methods in metabolomics. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}