{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:16:09Z","timestamp":1789146969989,"version":"build-2803163510"},"reference-count":0,"publisher":"Cold Spring Harbor Laboratory","funder":[{"DOI":"10.13039\/501100000272","name":"NIH","doi-asserted-by":"publisher","award":["RO1HL151388"],"award-info":[{"award-number":["RO1HL151388"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIH","doi-asserted-by":"publisher","award":["RO1HL162800"],"award-info":[{"award-number":["RO1HL162800"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIH","doi-asserted-by":"publisher","award":["R35GM158171"],"award-info":[{"award-number":["R35GM158171"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIH","doi-asserted-by":"publisher","award":["NEI R01EY032609"],"award-info":[{"award-number":["NEI R01EY032609"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"Brightfocus Foundation New Investigator","doi-asserted-by":"publisher","award":["M2021018N"],"award-info":[{"award-number":["M2021018N"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"ERC","doi-asserted-by":"publisher","award":["101141820"],"award-info":[{"award-number":["101141820"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"accepted":{"date-parts":[[2026,8,5]]},"abstract":"<jats:p>\n                    How mammalian organ size is precisely regulated remains incompletely understood. This process depends on the coordinated balance between cell proliferation, differentiation, and apoptosis. In the heart, the epicardium plays a central role in embryonic cardiac growth as a source of multiple cardiac progenitor lineages. The transcription factor\n                    <jats:italic>Wt1<\/jats:italic>\n                    is essential for epicardial development and maturation, and its loss disrupts epicardial maintenance and the generation of epicardial-derived cells (EPDCs). In addition, the epicardium produces mitogenic factors required for cardiomyocyte (CM) proliferation, including those of the insulin-like growth factor (\n                    <jats:italic>IGF<\/jats:italic>\n                    ) signaling pathway. Consistently, functional inactivation of\n                    <jats:italic>Igf1<\/jats:italic>\n                    or\n                    <jats:italic>Igf2<\/jats:italic>\n                    in mice results in severe prenatal growth reduction, with mutant embryos \u223c60% smaller than controls, underscoring the roles of these genes in organ and fetal growth. We recently identified the cardiac lymphatic vasculature as an unexpected regulator of heart size during embryonic development. Here, by combining single-cell RNA sequencing with loss-of-function mouse models, we uncover a critical regulatory network linking cardiac lymphatics, the epicardium,\n                    <jats:italic>Wt1<\/jats:italic>\n                    , and\n                    <jats:italic>Igf1<\/jats:italic>\n                    signaling that controls the final stages of embryonic cardiac growth. Our findings suggest that cardiac lymphatics act as a physiological quality control system for heart growth. Furthermore, using gain-of-function approaches in human epicardial organoids, we demonstrate that Reelin promotes epicardial fate, suggesting that the beneficial roles of lymphatics in adult cardiac repair are likely mediated through Reelin-dependent epicardial reactivation.\n                  <\/jats:p>","DOI":"10.1101\/gad.354151.126","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:05:19Z","timestamp":1789146319000},"source":"Crossref","is-referenced-by-count":0,"title":["Lymphatics-epicardial cross talk via Reelin controls cardiac growth"],"prefix":"10.1101","author":[{"given":"Yalu","family":"Zhou","sequence":"first","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Pascual","family":"El Bobakry","sequence":"additional","affiliation":[{"name":"Unidad Bioinformatica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain;"},{"name":"Universidad Aut\u00f3noma de Madrid, Madrid 28049, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Roy","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Torroja","sequence":"additional","affiliation":[{"name":"Unidad Bioinformatica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Dorn","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Madrid, Madrid 28049, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Zengerle","sequence":"additional","affiliation":[{"name":"Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, TUM University Hospital, Klinikum Rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich 81675, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Vidal-Cruchez","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics, Simpson Querrey Biomedical Research Center, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Kahn","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Liang","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Quaggin","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Moretti","sequence":"additional","affiliation":[{"name":"Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, TUM University Hospital, Klinikum Rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich 81675, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam","family":"Ben-Sahra","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics, Simpson Querrey Biomedical Research Center, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"},{"name":"Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Sosa-Pineda","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Oliver","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2026,9,11]]},"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.354151.126","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:05:20Z","timestamp":1789146320000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.354151.126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":0,"alternative-id":["10.1101\/gad.354151.126"],"URL":"https:\/\/doi.org\/10.1101\/gad.354151.126","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}