{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:05:25Z","timestamp":1793415925225,"version":"4.5.0"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-52221-9","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T16:02:39Z","timestamp":1726156959000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-5677","authenticated-orcid":false,"given":"Pengcheng","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixing","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Nimal","family":"Selvaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-2810","authenticated-orcid":false,"given":"Lincai","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gongxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3605-1429","authenticated-orcid":false,"given":"Lin","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-9066","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8128-5874","authenticated-orcid":false,"given":"Donghui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"52221_CR1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1093\/eurjpc\/zwab213","volume":"29","author":"S Safiri","year":"2022","unstructured":"Safiri, S. et al. Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990\u20132019. Eur. J. Prev. Cardiol. 29, 420\u2013431 (2022).","journal-title":"Eur. J. Prev. Cardiol."},{"key":"52221_CR2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.118.005375","volume":"12","author":"AN Nowbar","year":"2019","unstructured":"Nowbar, A. N., Gitto, M., Howard, J. P., Francis, D. P. & Al-Lamee, R. Mortality from ischemic heart disease. Circ. Cardiovasc Qual. Outcomes 12, e005375 (2019).","journal-title":"Circ. Cardiovasc Qual. Outcomes"},{"key":"52221_CR3","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41569-022-00799-2","volume":"20","author":"M Pesce","year":"2023","unstructured":"Pesce, M. et al. Cardiac fibroblasts and mechanosensation in heart development, health and disease. Nat. Rev. Cardiol. 20, 309\u2013324 (2023).","journal-title":"Nat. Rev. Cardiol."},{"key":"52221_CR4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12929-021-00722-w","volume":"28","author":"C Piamsiri","year":"2021","unstructured":"Piamsiri, C., Maneechote, C., Siri-Angkul, N., Chattipakorn, S. C. & Chattipakorn, N. Targeting necroptosis as therapeutic potential in chronic myocardial infarction. J. Biomed. Sci. 28, 25 (2021).","journal-title":"J. Biomed. Sci."},{"key":"52221_CR5","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1161\/01.CIR.77.3.589","volume":"77","author":"JM de Bakker","year":"1988","unstructured":"de Bakker, J. M. et al. Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation. Circulation 77, 589\u2013606 (1988).","journal-title":"Circulation"},{"key":"52221_CR6","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.pbiomolbio.2015.11.002","volume":"120","author":"JW Holmes","year":"2016","unstructured":"Holmes, J. W., Laksman, Z. & Gepstein, L. Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation. Prog. Biophys. Mol. Biol. 120, 134\u2013148 (2016).","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"52221_CR7","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/nprot.2012.150","volume":"8","author":"X Lian","year":"2013","unstructured":"Lian, X. et al. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt\/beta-catenin signaling under fully defined conditions. Nat. Protoc. 8, 162\u2013175 (2013).","journal-title":"Nat. Protoc."},{"key":"52221_CR8","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1161\/CIRCRESAHA.119.315491","volume":"125","author":"H Zhang","year":"2019","unstructured":"Zhang, H. et al. Generation of quiescent cardiac fibroblasts from human induced pluripotent stem cells for in vitro modeling of cardiac fibrosis. Circ. Res. 125, 552\u2013566 (2019).","journal-title":"Circ. Res"},{"key":"52221_CR9","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1161\/CIRCRESAHA.118.312913","volume":"123","author":"DT Paik","year":"2018","unstructured":"Paik, D. T. et al. Large-scale single-cell RNA-Seq reveals molecular signatures of heterogeneous populations of human induced pluripotent stem cell-derived endothelial cells. Circ. Res. 123, 443\u2013450 (2018).","journal-title":"Circ. Res."},{"key":"52221_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01946-x","volume":"8","author":"IY Shadrin","year":"2017","unstructured":"Shadrin, I. Y. et al. Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat. Commun. 8, 1825 (2017).","journal-title":"Nat. Commun."},{"key":"52221_CR11","doi-asserted-by":"publisher","first-page":"5813","DOI":"10.1016\/j.biomaterials.2013.04.026","volume":"34","author":"D Zhang","year":"2013","unstructured":"Zhang, D. et al. Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. Biomaterials 34, 5813\u20135820 (2013).","journal-title":"Biomaterials"},{"key":"52221_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25329-5","volume":"12","author":"YR Lewis-Israeli","year":"2021","unstructured":"Lewis-Israeli, Y. R. et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat. Commun. 12, 5142 (2021).","journal-title":"Nat. Commun."},{"key":"52221_CR13","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.1016\/j.cell.2021.04.034","volume":"184","author":"P Hofbauer","year":"2021","unstructured":"Hofbauer, P. et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 184, 3299\u20133317.e3222 (2021).","journal-title":"Cell"},{"key":"52221_CR14","first-page":"1118","volume":"144","author":"HK Voges","year":"2017","unstructured":"Voges, H. K. et al. Development of a human cardiac organoid injury model reveals innate regenerative potential. Development 144, 1118\u20131127 (2017).","journal-title":"Development"},{"key":"52221_CR15","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/s41551-020-0539-4","volume":"4","author":"DJ Richards","year":"2020","unstructured":"Richards, D. J. et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nat. Biomed. Eng. 4, 446\u2013462 (2020).","journal-title":"Nat. Biomed. Eng."},{"key":"52221_CR16","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/nprot.2016.031","volume":"11","author":"BD Polizzotti","year":"2016","unstructured":"Polizzotti, B. D., Ganapathy, B., Haubner, B. J., Penninger, J. M. & Kuhn, B. A cryoinjury model in neonatal mice for cardiac translational and regeneration research. Nat. Protoc. 11, 542\u2013552 (2016).","journal-title":"Nat. Protoc."},{"key":"52221_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s41231-017-0011-y","volume":"2","author":"A Hirano","year":"2017","unstructured":"Hirano, A. et al. Cryoinjury-induced acute myocardial infarction model and ameroid constrictor-induced ischemic heart disease model in adult micro-mini pigs for preclinical studies. Transl. Med. Commun. 2, 1 (2017).","journal-title":"Transl. Med. Commun."},{"key":"52221_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0355-7","volume":"51","author":"JN Peoples","year":"2019","unstructured":"Peoples, J. N., Saraf, A., Ghazal, N., Pham, T. T. & Kwong, J. Q. Mitochondrial dysfunction and oxidative stress in heart disease. Exp. Mol. Med. 51, 1\u201313 (2019).","journal-title":"Exp. Mol. Med"},{"key":"52221_CR19","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s00441-016-2431-9","volume":"365","author":"V Talman","year":"2016","unstructured":"Talman, V. & Ruskoaho, H. Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration. Cell Tissue Res. 365, 563\u2013581 (2016).","journal-title":"Cell Tissue Res"},{"key":"52221_CR20","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.addr.2021.03.021","volume":"173","author":"M Liu","year":"2021","unstructured":"Liu, M., Lopez de Juan Abad, B. & Cheng, K. Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies. Adv. Drug Deliv. Rev. 173, 504\u2013519 (2021).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"52221_CR21","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s44161-022-00043-7","volume":"1","author":"SLK Bowers","year":"2022","unstructured":"Bowers, S. L. K., Meng, Q. & Molkentin, J. D. Fibroblasts orchestrate cellular crosstalk in the heart through the ECM. Nat. Cardiovas. Res. 1, 312\u2013321 (2022).","journal-title":"Nat. Cardiovas. Res."},{"key":"52221_CR22","doi-asserted-by":"publisher","first-page":"708406","DOI":"10.3389\/fcvm.2021.708406","volume":"8","author":"ABP Noordman","year":"2021","unstructured":"Noordman, A. B. P. et al. Myocardial scar characterization and future ventricular arrhythmia in patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator. Front Cardiovasc Med. 8, 708406 (2021).","journal-title":"Front Cardiovasc Med"},{"key":"52221_CR23","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.19102\/icrm.2018.090201","volume":"9","author":"AH Bui","year":"2018","unstructured":"Bui, A. H. & Waks, J. W. Risk stratification of sudden cardiac death after acute myocardial infarction. J. Innov. Card. Rhythm Manag. 9, 3035\u20133049 (2018).","journal-title":"J. Innov. Card. Rhythm Manag."},{"key":"52221_CR24","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1124\/mol.112.083097","volume":"83","author":"J Sun","year":"2013","unstructured":"Sun, J. et al. Targeting the metastasis suppressor, NDRG1, using novel iron chelators: regulation of stress fiber-mediated tumor cell migration via modulation of the ROCK1\/pMLC2 signaling pathway. Mol. Pharm. 83, 454\u2013469 (2013).","journal-title":"Mol. Pharm."},{"key":"52221_CR25","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41419-022-04804-x","volume":"13","author":"HAN Soliman","year":"2022","unstructured":"Soliman, H. A. N., Toso, E. A., Darwish, I. E., Ali, S. M. & Kyba, M. Antiapoptotic Protein FAIM2 is targeted by miR-3202, and DUX4 via TRIM21, leading to cell death and defective myogenesis. Cell Death Dis. 13, 405 (2022).","journal-title":"Cell Death Dis."},{"key":"52221_CR26","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1093\/cvr\/cvaa324","volume":"117","author":"NG Frangogiannis","year":"2021","unstructured":"Frangogiannis, N. G. Cardiac fibrosis. Cardiovasc Res. 117, 1450\u20131488 (2021).","journal-title":"Cardiovasc Res"},{"key":"52221_CR27","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1161\/CIRCRESAHA.119.315862","volume":"126","author":"Y Guo","year":"2020","unstructured":"Guo, Y. & Pu, W. T. Cardiomyocyte maturation: new phase in development. Circ. Res. 126, 1086\u20131106 (2020).","journal-title":"Circ. Res."},{"key":"52221_CR28","doi-asserted-by":"publisher","first-page":"e110752","DOI":"10.1371\/journal.pone.0110752","volume":"9","author":"E Cagavi","year":"2014","unstructured":"Cagavi, E. et al. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation. PLoS One 9, e110752 (2014).","journal-title":"PLoS One"},{"key":"52221_CR29","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":"52221_CR30","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.cell.2018.02.014","volume":"173","author":"TMA Mohamed","year":"2018","unstructured":"Mohamed, T. M. A. et al. Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration. Cell 173, 104\u2013116.e112 (2018).","journal-title":"Cell"},{"key":"52221_CR31","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00395-021-00897-1","volume":"116","author":"M Rao","year":"2021","unstructured":"Rao, M. et al. Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level. Basic Res. Cardiol. 116, 55 (2021).","journal-title":"Basic Res. Cardiol."},{"key":"52221_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30630-y","volume":"13","author":"T Ko","year":"2022","unstructured":"Ko, T. et al. Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-beta-IGFBP7 axis. Nat. Commun. 13, 3275 (2022).","journal-title":"Nat. Commun."},{"key":"52221_CR33","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1016\/j.celrep.2019.01.079","volume":"26","author":"Y Cui","year":"2019","unstructured":"Cui, Y. et al. Single-cell transcriptome analysis maps the developmental track of the human heart. Cell Rep. 26, 1934\u20131950.e1935 (2019).","journal-title":"Cell Rep."},{"key":"52221_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24414-z","volume":"12","author":"P Quijada","year":"2021","unstructured":"Quijada, P. et al. Coordination of endothelial cell positioning and fate specification by the epicardium. Nat. Commun. 12, 4155 (2021).","journal-title":"Nat. Commun."},{"key":"52221_CR35","doi-asserted-by":"publisher","first-page":"e146926","DOI":"10.1172\/JCI146926","volume":"132","author":"C Humeres","year":"2022","unstructured":"Humeres, C. et al. Smad7 effects on TGF-beta and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure. J. Clin. Invest. 132, e146926 (2022).","journal-title":"J. Clin. Invest."},{"key":"52221_CR36","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/s44161-022-00183-w","volume":"1","author":"VR Knight-Schrijver","year":"2022","unstructured":"Knight-Schrijver, V. R. et al. A single-cell comparison of adult and fetal human epicardium defines the age-associated changes in epicardial activity. Nat. Cardiovasc. Res. 1, 1215\u20131229 (2022).","journal-title":"Nat. Cardiovasc. Res."},{"key":"52221_CR37","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1161\/CIRCRESAHA.119.315857","volume":"126","author":"P Quijada","year":"2020","unstructured":"Quijada, P., Trembley, M. A. & Small, E. M. The role of the epicardium during heart development and repair. Circ. Res. 126, 377\u2013394 (2020).","journal-title":"Circ. Res."},{"key":"52221_CR38","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1111\/j.1582-4934.2011.01450.x","volume":"15","author":"B Zhou","year":"2011","unstructured":"Zhou, B. & Pu, W. T. Epicardial epithelial-to-mesenchymal transition in injured heart. J. Cell Mol. Med. 15, 2781\u20132783 (2011).","journal-title":"J. Cell Mol. Med."},{"key":"52221_CR39","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nrd.2017.106","volume":"16","author":"TJ Cahill","year":"2017","unstructured":"Cahill, T. J., Choudhury, R. P. & Riley, P. R. Heart regeneration and repair after myocardial infarction: translational opportunities for novel therapeutics. Nat. Rev. Drug Discov. 16, 699\u2013717 (2017).","journal-title":"Nat. Rev. Drug Discov."},{"key":"52221_CR40","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.freeradbiomed.2007.12.007","volume":"44","author":"ED van Deel","year":"2008","unstructured":"van Deel, E. D. et al. Extracellular superoxide dismutase protects the heart against oxidative stress and hypertrophy after myocardial infarction. Free Radic. Biol. Med. 44, 1305\u20131313 (2008).","journal-title":"Free Radic. Biol. Med."},{"key":"52221_CR41","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.765","volume":"11","author":"Y Ye","year":"2023","unstructured":"Ye, Y. et al. PON2 ameliorates Ang II-induced cardiomyocyte injury by targeting the CANX\/NOX4 signaling pathway. Immun. Inflamm. Dis. 11, e765 (2023).","journal-title":"Immun. Inflamm. Dis."},{"key":"52221_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03699-4","volume":"12","author":"C Li","year":"2021","unstructured":"Li, C. et al. PXDN reduces autophagic flux in insulin-resistant cardiomyocytes via modulating FoxO1. Cell Death Dis. 12, 418 (2021).","journal-title":"Cell Death Dis."},{"key":"52221_CR43","doi-asserted-by":"publisher","first-page":"6549","DOI":"10.3390\/ijms23126549","volume":"23","author":"P Canale","year":"2022","unstructured":"Canale, P. et al. Role of miR-133\/Dio3 Axis in the T3-dependent modulation of cardiac mitoK-ATP Expression. Int J. Mol. Sci. 23, 6549 (2022).","journal-title":"Int J. Mol. Sci."},{"key":"52221_CR44","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/S0092-8674(00)81921-2","volume":"88","author":"L Leyns","year":"1997","unstructured":"Leyns, L., Bouwmeester, T., Kim, S. H., Piccolo, S. & De Robertis, E. M. Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. Cell 88, 747\u2013756 (1997).","journal-title":"Cell"},{"key":"52221_CR45","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.isci.2019.07.039","volume":"19","author":"H Lee","year":"2019","unstructured":"Lee, H. & Evans, T. TMEM88 inhibits Wnt signaling by promoting Wnt signalosome localization to multivesicular bodies. iScience 19, 267\u2013280 (2019).","journal-title":"iScience"},{"key":"52221_CR46","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1161\/CIRCRESAHA.111.259556","volume":"110","author":"G Heusch","year":"2012","unstructured":"Heusch, G. et al. STAT5 activation and cardioprotection by remote ischemic preconditioning in humans: short communication. Circ. Res. 110, 111\u2013115 (2012).","journal-title":"Circ. Res"},{"key":"52221_CR47","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1016\/j.devcel.2023.10.012","volume":"58","author":"M Cui","year":"2023","unstructured":"Cui, M. et al. Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development. Dev. Cell 58, 2867\u20132880.e2867 (2023).","journal-title":"Dev. Cell"},{"key":"52221_CR48","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/sj.cdd.4401586","volume":"12","author":"J Milia","year":"2005","unstructured":"Milia, J. et al. Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication. Cell Death Differ. 12, 492\u2013501 (2005).","journal-title":"Cell Death Differ."},{"key":"52221_CR49","doi-asserted-by":"publisher","first-page":"854540","DOI":"10.3389\/fnint.2022.854540","volume":"16","author":"MJ Li","year":"2022","unstructured":"Li, M. J. et al. Upregulation of CCNB2 and its perspective mechanisms in cerebral ischemic stroke and all subtypes of lung cancer: a comprehensive study. Front Integr. Neurosci. 16, 854540 (2022).","journal-title":"Front Integr. Neurosci."},{"key":"52221_CR50","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.yjmcc.2013.04.024","volume":"60","author":"X Wang","year":"2013","unstructured":"Wang, X. et al. LOX-1 in the maintenance of cytoskeleton and proliferation in senescent cardiac fibroblasts. J. Mol. Cell Cardiol. 60, 184\u2013190 (2013).","journal-title":"J. Mol. Cell Cardiol."},{"key":"52221_CR51","doi-asserted-by":"publisher","first-page":"e0158475","DOI":"10.1371\/journal.pone.0158475","volume":"11","author":"Y Zou","year":"2016","unstructured":"Zou, Y. et al. DNA Hypermethylation of CREB3L1 and Bcl-2 associated with the mitochondrial-mediated apoptosis via PI3K\/Akt pathway in human BEAS-2B cells exposure to silica nanoparticles. PLoS One 11, e0158475 (2016).","journal-title":"PLoS One"},{"key":"52221_CR52","doi-asserted-by":"publisher","first-page":"3511","DOI":"10.1093\/nar\/gkr1203","volume":"40","author":"B Westendorp","year":"2012","unstructured":"Westendorp, B. et al. E2F7 represses a network of oscillating cell cycle genes to control S-phase progression. Nucleic Acids Res. 40, 3511\u20133523 (2012).","journal-title":"Nucleic Acids Res."},{"key":"52221_CR53","doi-asserted-by":"publisher","first-page":"6869","DOI":"10.1080\/21655979.2021.1972194","volume":"12","author":"R Liao","year":"2021","unstructured":"Liao, R. et al. E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-beta1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene. Bioengineered 12, 6869\u20136877 (2021).","journal-title":"Bioengineered"},{"key":"52221_CR54","doi-asserted-by":"publisher","first-page":"dev185652","DOI":"10.1242\/dev.185652","volume":"147","author":"A Holowiecki","year":"2020","unstructured":"Holowiecki, A. et al. Pbx4 limits heart size and fosters arch artery formation by partitioning second heart field progenitors and restricting proliferation. Development 147, dev185652 (2020).","journal-title":"Development"},{"key":"52221_CR55","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s42003-023-04534-6","volume":"6","author":"M Stellato","year":"2023","unstructured":"Stellato, M. et al. The AP-1 transcription factor Fosl-2 drives cardiac fibrosis and arrhythmias under immunofibrotic conditions. Commun. Biol. 6, 161 (2023).","journal-title":"Commun. Biol."},{"key":"52221_CR56","doi-asserted-by":"publisher","first-page":"3520","DOI":"10.1172\/JCI42028","volume":"120","author":"P Teekakirikul","year":"2010","unstructured":"Teekakirikul, P. et al. Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-beta. J. Clin. Invest 120, 3520\u20133529 (2010).","journal-title":"J. Clin. Invest"},{"key":"52221_CR57","doi-asserted-by":"publisher","first-page":"149","DOI":"10.2119\/molmed.2011.00183","volume":"18","author":"GJ Zhao","year":"2012","unstructured":"Zhao, G. J., Yin, K., Fu, Y. C. & Tang, C. K. The interaction of ApoA-I and ABCA1 triggers signal transduction pathways to mediate efflux of cellular lipids. Mol. Med. 18, 149\u2013158 (2012).","journal-title":"Mol. Med"},{"key":"52221_CR58","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nature22979","volume":"547","author":"Y Morikawa","year":"2017","unstructured":"Morikawa, Y., Heallen, T., Leach, J., Xiao, Y. & Martin, J. F. Dystrophin-glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation. Nature 547, 227\u2013231 (2017).","journal-title":"Nature"},{"key":"52221_CR59","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s11897-020-00470-2","volume":"17","author":"DW Sorensen","year":"2020","unstructured":"Sorensen, D. W. & van Berlo, J. H. The role of TGF-beta signaling in cardiomyocyte proliferation. Curr. Heart Fail Rep. 17, 225\u2013233 (2020).","journal-title":"Curr. Heart Fail Rep."},{"key":"52221_CR60","doi-asserted-by":"publisher","first-page":"e160745","DOI":"10.1172\/jci.insight.160745","volume":"8","author":"J Zhou","year":"2023","unstructured":"Zhou, J. et al. The long noncoding RNA THBS1-AS1 promotes cardiac fibroblast activation in cardiac fibrosis by regulating TGFBR1. JCI Insight 8, e160745 (2023).","journal-title":"JCI Insight"},{"key":"52221_CR61","doi-asserted-by":"publisher","first-page":"101699","DOI":"10.1016\/j.redox.2020.101699","volume":"37","author":"Y Wang","year":"2020","unstructured":"Wang, Y. et al. Low density lipoprotein receptor related protein 6 (LRP6) protects heart against oxidative stress by the crosstalk of HSF1 and GSK3beta. Redox Biol. 37, 101699 (2020).","journal-title":"Redox Biol."},{"key":"52221_CR62","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.stemcr.2022.01.009","volume":"17","author":"H Yang","year":"2022","unstructured":"Yang, H. et al. Deriving waveform parameters from calcium transients in human iPSC-derived cardiomyocytes to predict cardiac activity with machine learning. Stem Cell Rep. 17, 556\u2013568 (2022).","journal-title":"Stem Cell Rep."},{"key":"52221_CR63","doi-asserted-by":"publisher","first-page":"733354","DOI":"10.3389\/fcell.2021.733354","volume":"9","author":"KA Peck","year":"2021","unstructured":"Peck, K. A. et al. Extracellular vesicles secreted by TDO2-augmented fibroblasts regulate pro-inflammatory response in macrophages. Front Cell Dev. Biol. 9, 733354 (2021).","journal-title":"Front Cell Dev. Biol."},{"key":"52221_CR64","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1074\/jbc.M116.727479","volume":"292","author":"A Kaur","year":"2017","unstructured":"Kaur, A. et al. ChaC2, an enzyme for slow turnover of cytosolic glutathione. J. Biol. Chem. 292, 638\u2013651 (2017).","journal-title":"J. Biol. Chem."},{"key":"52221_CR65","doi-asserted-by":"publisher","first-page":"81","DOI":"10.7150\/ijbs.28304","volume":"15","author":"H Pei","year":"2019","unstructured":"Pei, H. et al. G protein-coupled estrogen receptor 1 inhibits angiotensin II-induced cardiomyocyte hypertrophy via the regulation of PI3K-Akt-mTOR signalling and autophagy. Int J. Biol. Sci. 15, 81\u201392 (2019).","journal-title":"Int J. Biol. Sci."},{"key":"52221_CR66","doi-asserted-by":"publisher","first-page":"906586","DOI":"10.3389\/fendo.2022.906586","volume":"13","author":"V Duval","year":"2022","unstructured":"Duval, V., Alayrac, P., Silvestre, J. S. & Levoye, A. Emerging roles of the atypical chemokine receptor 3 (ACKR3) in cardiovascular diseases. Front Endocrinol. (Lausanne) 13, 906586 (2022).","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"52221_CR67","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/j.bbabio.2018.05.019","volume":"1859","author":"S Cadenas","year":"2018","unstructured":"Cadenas, S. Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim Biophys. Acta Bioenerg. 1859, 940\u2013950 (2018).","journal-title":"Biochim Biophys. Acta Bioenerg."},{"key":"52221_CR68","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1161\/CIRCULATIONAHA.122.060257","volume":"147","author":"W Cai","year":"2023","unstructured":"Cai, W. et al. Alox15\/15-HpETE aggravates myocardial ischemia-reperfusion injury by promoting cardiomyocyte ferroptosis. Circulation 147, 1444\u20131460 (2023).","journal-title":"Circulation"},{"key":"52221_CR69","doi-asserted-by":"publisher","first-page":"663655","DOI":"10.3389\/fphar.2021.663655","volume":"12","author":"I Voros","year":"2021","unstructured":"Voros, I. et al. Somatostatin and its receptors in myocardial ischemia\/reperfusion injury and cardioprotection. Front Pharm. 12, 663655 (2021).","journal-title":"Front Pharm."},{"key":"52221_CR70","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1161\/CIRCULATIONAHA.117.030801","volume":"137","author":"N Natarajan","year":"2018","unstructured":"Natarajan, N. et al. Complement receptor C5aR1 plays an evolutionarily conserved role in successful cardiac regeneration. Circulation 137, 2152\u20132165 (2018).","journal-title":"Circulation"},{"key":"52221_CR71","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s41569-018-0022-z","volume":"15","author":"ML Lindsey","year":"2018","unstructured":"Lindsey, M. L. Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling. Nat. Rev. Cardiol. 15, 471\u2013479 (2018).","journal-title":"Nat. Rev. Cardiol."},{"key":"52221_CR72","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1161\/CIRCRESAHA.120.317798","volume":"127","author":"F Meng","year":"2020","unstructured":"Meng, F. & Martin, J. F. Embryonic ECM Protein SLIT2 and NPNT promote postnatal cardiomyocyte cytokinesis. Circ. Res. 127, 908\u2013910 (2020).","journal-title":"Circ. Res."},{"key":"52221_CR73","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.stem.2019.05.020","volume":"25","author":"Y Zhou","year":"2019","unstructured":"Zhou, Y. et al. Single-cell transcriptomic analyses of cell fate transitions during human cardiac reprogramming. Cell Stem Cell 25, 149\u2013164.e149 (2019).","journal-title":"Cell Stem Cell"},{"key":"52221_CR74","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1161\/CIRCULATIONAHA.106.659037","volume":"115","author":"Y Asaumi","year":"2007","unstructured":"Asaumi, Y. et al. Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice. Circulation 115, 2022\u20132032 (2007).","journal-title":"Circulation"},{"key":"52221_CR75","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1161\/CIRCULATIONAHA.118.033648","volume":"138","author":"NT Lam","year":"2018","unstructured":"Lam, N. T. & Sadek, H. A. Neonatal heart regeneration: comprehensive literature review. Circulation 138, 412\u2013423 (2018).","journal-title":"Circulation"},{"key":"52221_CR76","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.stem.2016.10.005","volume":"20","author":"ICL Pillai","year":"2017","unstructured":"Pillai, I. C. L. et al. Cardiac fibroblasts adopt osteogenic fates and can be targeted to attenuate pathological heart calcification. Cell Stem Cell 20, 218\u2013232.e215 (2017).","journal-title":"Cell Stem Cell"},{"key":"52221_CR77","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/j.1476-5381.2010.00725.x","volume":"160","author":"J Giacomotto","year":"2010","unstructured":"Giacomotto, J. & Segalat, L. High-throughput screening and small animal models, where are we? Br. J. Pharm. 160, 204\u2013216 (2010).","journal-title":"Br. J. Pharm."},{"key":"52221_CR78","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/nature13839","volume":"514","author":"E Ubil","year":"2014","unstructured":"Ubil, E. et al. Mesenchymal-endothelial transition contributes to cardiac neovascularization. Nature 514, 585\u2013590 (2014).","journal-title":"Nature"},{"key":"52221_CR79","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s44161-022-00028-6","volume":"1","author":"AL Koenig","year":"2022","unstructured":"Koenig, A. L. et al. Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. Nat. Cardiovasc Res. 1, 263\u2013280 (2022).","journal-title":"Nat. Cardiovasc Res"},{"key":"52221_CR80","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12260","volume":"7","author":"O Kanisicak","year":"2016","unstructured":"Kanisicak, O. et al. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat. Commun. 7, 12260 (2016).","journal-title":"Nat. Commun."},{"key":"52221_CR81","first-page":"1911","volume":"43","author":"LY Dong","year":"2019","unstructured":"Dong, L. Y., Qiu, X. X., Zhuang, Y. & Xue, S. Y-27632, a Rho-kinase inhibitor, attenuates myocardial ischemia-reperfusion injury in rats. Int J. Mol. Med. 43, 1911\u20131919 (2019).","journal-title":"Int J. Mol. Med"},{"key":"52221_CR82","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1093\/cvr\/cvy207","volume":"115","author":"M Zhao","year":"2019","unstructured":"Zhao, M. et al. Y-27632 preconditioning enhances transplantation of human-induced pluripotent stem cell-derived cardiomyocytes in myocardial infarction mice. Cardiovasc Res. 115, 343\u2013356 (2019).","journal-title":"Cardiovasc Res"},{"key":"52221_CR83","doi-asserted-by":"publisher","first-page":"113174","DOI":"10.1016\/j.celrep.2023.113174","volume":"42","author":"Y Xu","year":"2023","unstructured":"Xu, Y. et al. A transient wave of Bhlhe41(+) resident macrophages enables remodeling of the developing infarcted myocardium. Cell Rep. 42, 113174 (2023).","journal-title":"Cell Rep."},{"key":"52221_CR84","doi-asserted-by":"publisher","first-page":"E8372","DOI":"10.1073\/pnas.1707316114","volume":"114","author":"RJ Mills","year":"2017","unstructured":"Mills, R. J. et al. Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc. Natl Acad. Sci. USA 114, E8372\u2013E8381 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"52221_CR85","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-019-0709-6","volume":"17","author":"H Ruan","year":"2019","unstructured":"Ruan, H. et al. Single-cell reconstruction of differentiation trajectory reveals a critical role of ETS1 in human cardiac lineage commitment. BMC Biol. 17, 89 (2019).","journal-title":"BMC Biol."},{"key":"52221_CR86","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39369-y","volume":"13","author":"C Hall","year":"2023","unstructured":"Hall, C. et al. Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype. Sci. Rep. 13, 12137 (2023).","journal-title":"Sci. Rep."},{"key":"52221_CR87","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41569-021-00646-w","volume":"19","author":"NG Frangogiannis","year":"2022","unstructured":"Frangogiannis, N. G. Transforming growth factor-beta in myocardial disease. Nat. Rev. Cardiol. 19, 435\u2013455 (2022).","journal-title":"Nat. Rev. Cardiol."},{"key":"52221_CR88","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nmeth.2840","volume":"11","author":"Y Miyaoka","year":"2014","unstructured":"Miyaoka, Y. et al. Isolation of single-base genome-edited human iPS cells without antibiotic selection. Nat. Methods 11, 291\u2013293 (2014).","journal-title":"Nat. Methods"},{"key":"52221_CR89","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41421-022-00446-7","volume":"8","author":"L Li","year":"2022","unstructured":"Li, L. et al. Generation of high-performance human cardiomyocytes and engineered heart tissues from extended pluripotent stem cells. Cell Discov. 8, 105 (2022).","journal-title":"Cell Discov."},{"key":"52221_CR90","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/cr.2009.28","volume":"19","author":"D Zhang","year":"2009","unstructured":"Zhang, D. et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res. 19, 429\u2013438 (2009).","journal-title":"Cell Res"},{"key":"52221_CR91","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1161\/CIRCULATIONAHA.119.039711","volume":"140","author":"SJ Park","year":"2019","unstructured":"Park, S. J. et al. Insights into the pathogenesis of catecholaminergic polymorphic ventricular tachycardia from engineered human heart tissue. Circulation 140, 390\u2013404 (2019).","journal-title":"Circulation"},{"key":"52221_CR92","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1161\/CIRCRESAHA.122.321036","volume":"131","author":"J Pei","year":"2022","unstructured":"Pei, J. et al. LPA(2) contributes to vascular endothelium homeostasis and cardiac remodeling after myocardial infarction. Circ. Res. 131, 388\u2013403 (2022).","journal-title":"Circ. Res"},{"key":"52221_CR93","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-30196-9","volume":"13","author":"A Remes","year":"2023","unstructured":"Remes, A. et al. Adapted clustering method for generic analysis of histological fibrosis staining as an open source tool. Sci. Rep. 13, 4389 (2023).","journal-title":"Sci. Rep."},{"key":"52221_CR94","doi-asserted-by":"publisher","first-page":"16234","DOI":"10.1021\/acsnano.2c05168","volume":"16","author":"C Yu","year":"2022","unstructured":"Yu, C. et al. An intrapericardial injectable hydrogel patch for mechanical-electrical coupling with infarcted myocardium. ACS Nano 16, 16234\u201316248 (2022).","journal-title":"ACS Nano"},{"key":"52221_CR95","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411\u2013420 (2018).","journal-title":"Nat. Biotechnol."},{"key":"52221_CR96","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","volume":"20","author":"D Aran","year":"2019","unstructured":"Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163\u2013172 (2019).","journal-title":"Nat. Immunol."},{"key":"52221_CR97","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":"52221_CR98","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":"52221_CR99","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","volume":"15","author":"M Efremova","year":"2020","unstructured":"Efremova, M., Vento-Tormo, M., Teichmann, S. A. & Vento-Tormo, R. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc. 15, 1484\u20131506 (2020).","journal-title":"Nat. Protoc."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52221-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52221-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52221-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T17:03:06Z","timestamp":1726160586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52221-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,12]]},"references-count":99,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["52221"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-52221-9","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,12]]},"assertion":[{"value":"3 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"For the development of the hEHT injury model and its application in drug screening, we have been granted a Chinese patent, with inventors Donghui Zhang, Pengcheng Yang, and Jixing Gong, and patent number ZL 2020 1 0620164. X. Besides that, the authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7996"}}