{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:44:12Z","timestamp":1787687052864,"version":"build-2784847793"},"reference-count":72,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6646","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2023,5,19]]},"abstract":"<jats:p>Zebrafish hearts can regenerate by replacing damaged tissue with new cardiomyocytes. Although the steps leading up to the proliferation of surviving cardiomyocytes have been extensively studied, little is known about the mechanisms that control proliferation and redifferentiation to a mature state. We found that the cardiac dyad, a structure that regulates calcium handling and excitation-contraction coupling, played a key role in the redifferentiation process. A component of the cardiac dyad called leucine-rich repeat\u2013containing 10 (Lrrc10) acted as a negative regulator of proliferation, prevented cardiomegaly, and induced redifferentiation. We found that its function was conserved in mammalian cardiomyocytes. This study highlights the importance of the underlying mechanisms required for heart regeneration and their application to the generation of fully functional cardiomyocytes.<\/jats:p>","DOI":"10.1126\/science.abo6718","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T17:58:45Z","timestamp":1684432725000},"page":"758-764","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":50,"title":["Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration"],"prefix":"10.1126","volume":"380","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-3276","authenticated-orcid":true,"given":"Phong D.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8435-5578","authenticated-orcid":true,"given":"Iris","family":"Gooijers","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4688-4991","authenticated-orcid":true,"given":"Giulia","family":"Campostrini","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-834X","authenticated-orcid":true,"given":"Arie O.","family":"Verkerk","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam University Medical Center, Amsterdam, Netherlands."},{"name":"Department of Experimental Cardiology, University of Amsterdam, Amsterdam University Medical Center, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hessel","family":"Honkoop","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0038-6102","authenticated-orcid":true,"given":"Mara","family":"Bouwman","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7373-0093","authenticated-orcid":true,"given":"Dennis E. M.","family":"de Bakker","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."},{"name":"Leibniz Institute on Aging \u2013 Fritz Lipmann Institute (FLI), Jena, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-3285","authenticated-orcid":true,"given":"Tim","family":"Koopmans","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."},{"name":"Department of Animal Physiology, Osnabrueck University, Osnabr\u00fcck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-8788","authenticated-orcid":true,"given":"Aryan","family":"Vink","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerda E. M.","family":"Lamers","sequence":"additional","affiliation":[{"name":"Core Facility Microscopy, Institute of Biology, Leiden University, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-7145","authenticated-orcid":true,"given":"Avraham","family":"Shakked","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5904-2235","authenticated-orcid":true,"given":"Jonas","family":"Mars","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4779-099X","authenticated-orcid":true,"given":"Aat A.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Chocron","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3070-4389","authenticated-orcid":true,"given":"Kerstin","family":"Bartscherer","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."},{"name":"Department of Animal Physiology, Osnabrueck University, Osnabr\u00fcck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-9426","authenticated-orcid":true,"given":"Eldad","family":"Tzahor","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4549-6535","authenticated-orcid":true,"given":"Christine L.","family":"Mummery","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-6491","authenticated-orcid":true,"given":"Teun P.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5380-6743","authenticated-orcid":true,"given":"Milena","family":"Bellin","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands."},{"name":"Department of Biology, University of Padua, Padua, Italy."},{"name":"Veneto Institute of Molecular Medicine, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9418-0422","authenticated-orcid":true,"given":"Jeroen","family":"Bakkers","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands."},{"name":"Department of Pediatric Cardiology, Division of Pediatrics, University Medical Center Utrecht, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam5894"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077857"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-017-0027-y"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200708"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208863110"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aao5553"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05871"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3149"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00588-4"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.01.017"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313192110"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50163"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08804"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-11-21"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.12.010"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201949752"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.316167"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.08.052"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4162"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13233"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19815"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-023-00250-w"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1191-6"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08899"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11045"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2020.12.004"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310230"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00178"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12354"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02650-6"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0249"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4402"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.060897"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018503"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.006428"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043434"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.072"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3843"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051621"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.05.004"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2013"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00717.2014"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21225"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.04.039"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.01.001"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe2762"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.059345"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21343"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1177\/0023677219869037"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006596"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng875"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.26108"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2016.09.002"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0938-8"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55792"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00188-2"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202673"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.4.691"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038944"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419553111"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00497-2"},{"key":"e_1_3_3_67_2","doi-asserted-by":"crossref","unstructured":"C. W. van den Berg D. A. Elliott S. R. Braam C. L. Mummery R. P. Davis in Patient-Specific Induced Pluripotent Stem Cell Models: Generation and Characterization A. Nagy K. Turksen Eds. vol. 1353 of Methods in Molecular Biology (Humana Press 2014) pp. 163\u2013180.","DOI":"10.1007\/7651_2014_178"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.3791\/55587"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1603-1"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.462"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19539-z"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201201140"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.abo6718","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:09:58Z","timestamp":1705363798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.abo6718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":72,"journal-issue":{"issue":"6646","published-print":{"date-parts":[[2023,5,19]]}},"alternative-id":["10.1126\/science.abo6718"],"URL":"https:\/\/doi.org\/10.1126\/science.abo6718","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]},"assertion":[{"value":"2022-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}