{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:33:04Z","timestamp":1787567584731,"version":"build-2736575974"},"reference-count":62,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R35HL150713"],"award-info":[{"award-number":["R35HL150713"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL164013"],"award-info":[{"award-number":["R01HL164013"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL134764"],"award-info":[{"award-number":["U01HL134764"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R01EB032726"],"award-info":[{"award-number":["R01EB032726"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK134408"],"award-info":[{"award-number":["R01DK134408"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Tissue regeneration enhancer elements (TREEs) direct expression of target genes in injured and regenerating tissues. Additionally, TREEs of zebrafish origin were shown to direct expression of transgenes in border zone regions after cardiac injury when packaged into recombinant adeno-associated viral (AAV) vectors and introduced into mice. Future implementation of TREEs into AAV-based vectors as research tools and potential gene therapy modalities requires a deeper understanding of expression dynamics and potential off-target effects. Here, we applied in vivo bioluminescent imaging to mice systemically injected with AAV vectors containing different combinations of capsids, enhancers, and timing of delivery. Longitudinal tracking of expression directed by different TREEs revealed distinct amplitudes and durations of reporter gene expression in the injured heart. The liver-de-targeted AAV capsid, AAV.cc84, could deliver TREEs either pre- or post-cardiac injury to negate off-target expression in the liver while maintaining transduction in the heart. By screening AAV9-based capsid libraries dosed systemically in mice post-cardiac injury, we discovered a new capsid variant, AAV.IR41, with enhanced transduction in cardiac injuries and with elevated transduction of TREE-driven transgenes versus conventional AAV9 vectors. In vivo bioluminescence imaging offers insights into how enhancers and engineered capsids can be implemented to modulate spatiotemporal transgene expression for targeted therapies.<\/jats:p>","DOI":"10.7554\/elife.107148","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T10:30:41Z","timestamp":1749810641000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.107148","source":"Crossref","is-referenced-by-count":1,"title":["Spatial and longitudinal tracking of enhancer-AAV vectors that target transgene expression to injured mouse myocardium"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3850-3925","authenticated-orcid":true,"given":"David W","family":"Wolfson","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell Biology, Duke Regeneration Center, Duke University School of Medicine","place":["Durham, United States"]},{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, Duke University School of Medicine","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Joshua A","family":"Hull","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, Duke University School of Medicine","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Yongwu","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Engineering, Duke University","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Trevor J","family":"Gonzalez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, Duke University School of Medicine","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Mourya D","family":"Jayaram","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, Duke University School of Medicine","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Garth W","family":"Devlin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, Duke University School of Medicine","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Valentina","family":"Cigliola","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell Biology, Duke Regeneration Center, Duke University School of Medicine","place":["Durham, United States"]},{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology, Vanderbilt University","place":["Nashville, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Kelsey A","family":"Oonk","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell Biology, Duke Regeneration Center, Duke University School of Medicine","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Alan","family":"Rosales","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Engineering, Duke University","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5688-6061","authenticated-orcid":true,"given":"Nenad","family":"Bursac","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Engineering, Duke University","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Aravind","family":"Asokan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, Duke University School of Medicine","place":["Durham, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6743-5709","authenticated-orcid":true,"given":"Kenneth D","family":"Poss","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell Biology, Duke Regeneration Center, Duke University School of Medicine","place":["Durham, United States"]},{"id":[{"id":"https:\/\/ror.org\/05cb4rb43","id-type":"ROR","asserted-by":"publisher"}],"name":"Morgridge Institute for Research","place":["Madison, United States"]},{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell and Regenerative Biology, University of Wisconsin-Madison","place":["Madison, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1172\/JCI72181","type":"journal-article","article-title":"Macrophages are required for neonatal heart regeneration","volume":"124","author":"Aurora","year":"2014","journal-title":"The Journal of Clinical Investigation"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature22978","type":"journal-article","article-title":"The extracellular matrix protein agrin promotes heart regeneration in mice","volume":"547","author":"Bassat","year":"2017","journal-title":"Nature"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.cell.2009.04.060","type":"journal-article","article-title":"Neuregulin1\/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury","volume":"138","author":"Bersell","year":"2009","journal-title":"Cell"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200133","type":"journal-article","article-title":"Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration","volume":"149","author":"Cao","year":"2022","journal-title":"Development"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1126\/science.abg5159","type":"journal-article","article-title":"Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice","volume":"373","author":"Chen","year":"2021","journal-title":"Science"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1242\/dev.088526","type":"journal-article","article-title":"In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration","volume":"140","author":"Choi","year":"2013","journal-title":"Development"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40486-5","type":"journal-article","article-title":"Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer","volume":"14","author":"Cigliola","year":"2023","journal-title":"Nature Communications"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/ncb3149","type":"journal-article","article-title":"ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation","volume":"17","author":"D\u2019Uva","year":"2015","journal-title":"Nature Cell Biology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature11739","type":"journal-article","article-title":"Functional screening identifies miRNAs inducing cardiac regeneration","volume":"492","author":"Eulalio","year":"2012","journal-title":"Nature"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"13416","DOI":"10.1073\/pnas.1309810110","type":"journal-article","article-title":"Translational profiling of cardiomyocytes identifies an early Jak1\/Stat3 injury response required for zebrafish heart regeneration","volume":"110","author":"Fang","year":"2013","journal-title":"PNAS"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6173","type":"journal-article","article-title":"Acoel genome reveals the regulatory landscape of whole-body regeneration","volume":"363","author":"Gehrke","year":"2019","journal-title":"Science"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05871","type":"journal-article","article-title":"Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish","volume":"4","author":"Gemberling","year":"2015","journal-title":"eLife"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.devcel.2017.01.013","type":"journal-article","article-title":"Resolving heart regeneration by replacement histone profiling","volume":"40","author":"Goldman","year":"2017","journal-title":"Developmental Cell"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33745-4","type":"journal-article","article-title":"Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing","volume":"13","author":"Gonzalez","year":"2022","journal-title":"Nature Communications"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1038\/s41596-023-00875-y","type":"journal-article","article-title":"Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery","volume":"18","author":"Gonzalez","year":"2023","journal-title":"Nature Protocols"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11588","type":"journal-article","article-title":"Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs","volume":"5","author":"Harris","year":"2016","journal-title":"eLife"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58305","type":"journal-article","article-title":"Damage-responsive, maturity-silenced enhancers regulate multiple genes that direct regeneration in Drosophila","volume":"9","author":"Harris","year":"2020","journal-title":"eLife"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"4683","DOI":"10.1242\/dev.102798","type":"journal-article","article-title":"Hippo signaling impedes adult heart regeneration","volume":"140","author":"Heallen","year":"2013","journal-title":"Development"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1126\/science.aar2038","type":"journal-article","article-title":"Evidence for hormonal control of heart regenerative capacity during endothermy acquisition","volume":"364","author":"Hirose","year":"2019","journal-title":"Science"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.devcel.2017.11.010","type":"journal-article","article-title":"Zebrafish regulatory T cells mediate organ-specific regenerative programs","volume":"43","author":"Hui","year":"2017","journal-title":"Developmental Cell"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100170","type":"journal-article","article-title":"A regulatory network of Sox and Six transcription factors initiate a cell fate transformation during hearing regeneration in adult zebrafish","volume":"2","author":"Jimenez","year":"2022","journal-title":"Cell Genomics"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"32602","DOI":"10.1074\/jbc.M500684200","type":"journal-article","article-title":"Genetic inhibition or activation of JNK1\/2 protects the myocardium from ischemia-reperfusion-induced cell death in vivo","volume":"280","author":"Kaiser","year":"2005","journal-title":"The Journal of Biological Chemistry"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/nature17644","type":"journal-article","article-title":"Modulation of tissue repair by regeneration enhancer elements","volume":"532","author":"Kang","year":"2016","journal-title":"Nature"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"13255","DOI":"10.1073\/pnas.1511209112","type":"journal-article","article-title":"Myocardial NF-\u03baB activation is essential for zebrafish heart regeneration","volume":"112","author":"Karra","year":"2015","journal-title":"PNAS"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/j.devcel.2024.05.002","type":"journal-article","article-title":"A chromatin code for limb segment identity in axolotl limb regeneration","volume":"59","author":"Kawaguchi","year":"2024","journal-title":"Developmental Cell"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.devcel.2011.01.010","type":"journal-article","article-title":"Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration","volume":"20","author":"Kikuchi","year":"2011","journal-title":"Developmental Cell"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"17206","DOI":"10.1073\/pnas.0915016107","type":"journal-article","article-title":"PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts","volume":"107","author":"Kim","year":"2010","journal-title":"PNAS"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1002\/jgm.2673","type":"journal-article","article-title":"Adeno-associated virus serotype 9 administered systemically after reperfusion preferentially targets cardiomyocytes in the infarct border zone with pharmacodynamics suitable for the attenuation of left ventricular remodeling","volume":"14","author":"Konkalmatt","year":"2012","journal-title":"The Journal of Gene Medicine"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nature24045","type":"journal-article","article-title":"Hippo pathway deficiency reverses systolic heart failure after infarction","volume":"550","author":"Leach","year":"2017","journal-title":"Nature"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.cell.2006.08.052","type":"journal-article","article-title":"A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration","volume":"127","author":"Lepilina","year":"2006","journal-title":"Cell"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.stem.2023.01.009","type":"journal-article","article-title":"Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers","volume":"30","author":"Li","year":"2023","journal-title":"Cell Stem Cell"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nature12054","type":"journal-article","article-title":"Meis1 regulates postnatal cardiomyocyte cell cycle arrest","volume":"497","author":"Mahmoud","year":"2013","journal-title":"Nature"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.devcel.2015.06.017","type":"journal-article","article-title":"Nerves regulate cardiomyocyte proliferation and heart regeneration","volume":"34","author":"Mahmoud","year":"2015","journal-title":"Developmental Cell"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.devcel.2019.01.017","type":"journal-article","article-title":"YAP partially reprograms chromatin accessibility to directly induce adult cardiogenesis in vivo","volume":"48","author":"Monroe","year":"2019","journal-title":"Developmental Cell"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005781","type":"journal-article","article-title":"Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice","volume":"8","author":"Morikawa","year":"2015","journal-title":"Science Signaling"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nature22979","type":"journal-article","article-title":"Dystrophin-glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation","volume":"547","author":"Morikawa","year":"2017","journal-title":"Nature"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nature20173","type":"journal-article","article-title":"Hypoxia induces heart regeneration in adult mice","volume":"541","author":"Nakada","year":"2017","journal-title":"Nature"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1126\/science.abo6718","type":"journal-article","article-title":"Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration","volume":"380","author":"Nguyen","year":"2023","journal-title":"Science"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.cell.2022.12.022","type":"journal-article","article-title":"An evolved AAV variant enables efficient genetic engineering of murine T cells","volume":"186","author":"Nyberg","year":"2023","journal-title":"Cell"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.immuni.2025.01.009","type":"journal-article","article-title":"In vivo engineering of murine T cells using the evolved adeno-associated virus variant Ark313","volume":"58","author":"Nyberg","year":"2025","journal-title":"Immunity"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1126\/science.abe2762","type":"journal-article","article-title":"Kr\u00fcppel-like factor 1 is a core cardiomyogenic trigger in zebrafish","volume":"372","author":"Ogawa","year":"2021","journal-title":"Science"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ydbio.2024.01.011","type":"journal-article","article-title":"Neutrophils facilitate the epicardial regenerative response after zebrafish heart injury","volume":"508","author":"Peterson","year":"2024","journal-title":"Developmental Biology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1038\/s41551-024-01341-0","type":"journal-article","article-title":"Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries","volume":"9","author":"Rosales","year":"2025","journal-title":"Nature Biomedical Engineering"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54060-0","type":"journal-article","article-title":"Harnessing the regenerative potential of interleukin11 to enhance heart repair","volume":"15","author":"Shin","year":"2024","journal-title":"Nature Communications"},{"key":"bib45","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24635","type":"journal-article","article-title":"Dissection of zebrafish shha function using site-specific targeting with a Cre-dependent genetic switch","volume":"6","author":"Sugimoto","year":"2017","journal-title":"eLife"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41556-022-00906-y","type":"journal-article","article-title":"Enhancer selection dictates gene expression responses in remote organs during tissue regeneration","volume":"24","author":"Sun","year":"2022","journal-title":"Nature Cell Biology"},{"key":"bib47","doi-asserted-by":"publisher","DOI":"10.1242\/dev.202166","type":"journal-article","article-title":"Inter-organ communication during tissue regeneration","volume":"150","author":"Sun","year":"2023","journal-title":"Development"},{"key":"bib48","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114092","type":"journal-article","article-title":"ptx3a+ fibroblast\/epicardial cells provide a transient macrophage niche to promote heart regeneration","volume":"43","author":"Sun","year":"2024","journal-title":"Cell Reports"},{"key":"bib49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204338119","type":"journal-article","article-title":"Adrenergic receptor signaling induced by Klf15, a regulator of regeneration enhancer, promotes kidney reconstruction","volume":"119","author":"Suzuki","year":"2022","journal-title":"PNAS"},{"key":"bib50","doi-asserted-by":"publisher","DOI":"10.1242\/dev.191262","type":"journal-article","article-title":"Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration","volume":"147","author":"Thompson","year":"2020","journal-title":"Development"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"4285","DOI":"10.1172\/JCI81870","type":"journal-article","article-title":"Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload","volume":"127","author":"Toischer","year":"2017","journal-title":"The Journal of Clinical Investigation"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1101\/gr.233098.117","type":"journal-article","article-title":"Damage-responsive elements in Drosophila regeneration","volume":"28","author":"Vizcaya-Molina","year":"2018","journal-title":"Genome Research"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1073\/pnas.1116136109","type":"journal-article","article-title":"YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy","volume":"109","author":"von Gise","year":"2012","journal-title":"PNAS"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature14325","type":"journal-article","article-title":"Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling","volume":"522","author":"Wang","year":"2015","journal-title":"Nature"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz3090","type":"journal-article","article-title":"Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates","volume":"369","author":"Wang","year":"2020","journal-title":"Science"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.devcel.2023.12.012","type":"journal-article","article-title":"Distinct epicardial gene regulatory programs drive development and regeneration of the zebrafish heart","volume":"59","author":"Weinberger","year":"2024","journal-title":"Developmental Cell"},{"key":"bib57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35433-9","type":"journal-article","article-title":"Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration","volume":"13","author":"Xia","year":"2022","journal-title":"Nature Communications"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"13839","DOI":"10.1073\/pnas.1313192110","type":"journal-article","article-title":"Hippo pathway effector Yap promotes cardiac regeneration","volume":"110","author":"Xin","year":"2013","journal-title":"PNAS"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.stem.2022.11.012","type":"journal-article","article-title":"An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair","volume":"30","author":"Yan","year":"2023","journal-title":"Cell Stem Cell"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.celrep.2018.12.048","type":"journal-article","article-title":"Endocardial notch signaling promotes cardiomyocyte proliferation in the regenerating zebrafish heart through wnt pathway antagonism","volume":"26","author":"Zhao","year":"2019","journal-title":"Cell Reports"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh5313","type":"journal-article","article-title":"An injury-responsive mmp14b enhancer is required for heart regeneration","volume":"9","author":"Zlatanova","year":"2023","journal-title":"Science Advances"},{"key":"dataset1","doi-asserted-by":"publisher","DOI":"10.5061\/dryad.2547d7x4p","type":"dataset","article-title":"Data from: Spatial and longitudinal tracking of enhancer-AAV vectors that target transgene expression to injured mouse myocardium","volume-title":"Dryad Digital Repository","author":"Wolfson","year":"2026","unstructured":"Wolfson D, Hull J, Li Y, Gonzalez T, Jayaram M, Devlin G. 2026. Data from: Spatial and longitudinal tracking of enhancer-AAV vectors that target transgene expression to injured mouse myocardium. Dryad Digital Repository."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/107148\/elife-107148-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/107148\/elife-107148-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/107148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:27:01Z","timestamp":1787563621000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/107148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":62,"alternative-id":["10.7554\/eLife.107148"],"URL":"https:\/\/doi.org\/10.7554\/elife.107148","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.04.28.651096","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2025.04.28.651096","asserted-by":"object"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.107148.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.107148.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.107148.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"doi","id":"10.5061\/dryad.2547d7x4p","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP107148"}}