{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:15:11Z","timestamp":1781734511866,"version":"3.54.5"},"posted":{"date-parts":[[2024,12,11]]},"group-title":"Bioengineering","reference-count":187,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Neural crest cells (NCCs) are a multipotent embryonic cell population of ectodermal origin that extensively migrate during early development and contribute to the formation of multiple tissues. Cardiac NCCs play a critical role in heart development by orchestrating outflow tract septation, valve formation, aortic arch artery patterning, parasympathetic innervation, and maturation of the cardiac conduction system. Abnormal migration, proliferation, or differentiation of cardiac NCCs can lead to severe congenital cardiovascular malformations. However, the complexity and timing of early embryonic heart development pose significant challenges to studying the molecular mechanisms underlying NCC-related cardiac pathologies. Here, we present a sophisticated functional model of human heart assembloids derived from induced pluripotent stem cells, which, for the first time, recapitulates cardiac NCC integration into the human embryonic heart\n                  <jats:italic>in vitro<\/jats:italic>\n                  . NCCs successfully integrated at developmentally relevant stages into heart organoids, and followed developmental trajectories known to occur in the human heart. They demonstrated extensive migration, differentiated into cholinergic neurons capable of generating nerve impulses, and formed mature glial cells. Additionally, they contributed to the mesenchymal populations of the developing outflow tract. Through transcriptomic analysis, we revealed that NCCs acquire molecular features of their cardiac derivatives as heart assembloids develop. NCC-derived parasympathetic neurons formed functional connections with cardiomyocytes, promoting the maturation of the cardiac conduction system. Leveraging this model\u2019s cellular complexity and functional maturity, we uncovered that early exposure of NCCs to antidepressants harms the development of NCC derivatives in the context of the developing heart. The commonly prescribed antidepressant Paroxetine disrupted the expression of a critical early neuronal transcription factor, resulting in impaired parasympathetic innervation and functional deficits in cardiac tissue. This advanced heart assembloid model holds great promise for high-throughput drug screening and unraveling the molecular mechanisms underlying NCC-related cardiac formation and congenital heart defects.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IN BRIEF<\/jats:title>\n                  <jats:p>Human neural crest heart assembloids resembling the major directions of neural crest differentiation in the human embryonic heart, including parasympathetic innervation and the mesenchymal component of the outflow tract, provide a human-relevant embryonic platform for studying congenital heart defects and drug safety.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.12.11.627627","type":"posted-content","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T23:02:38Z","timestamp":1734044558000},"source":"Crossref","is-referenced-by-count":2,"title":["Self-organizing human heart assembloids with autologous and developmentally relevant cardiac neural crest-derived tissues"],"prefix":"10.64898","author":[{"given":"Aleksandra","family":"Kostina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Kiselev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"Lankerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sammantha","family":"Caywood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"Jurado-Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Volmert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"O\u2019Hern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniwat","family":"Juhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8329-5104","authenticated-orcid":false,"given":"Sangbum","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1383-2792","authenticated-orcid":false,"given":"Aitor","family":"Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024121402303576000_2024.12.11.627627v1.1","doi-asserted-by":"publisher","DOI":"10.5334\/gh.1288"},{"key":"2024121402303576000_2024.12.11.627627v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01886-7"},{"key":"2024121402303576000_2024.12.11.627627v1.3","unstructured":"National Center for Health Statistics. Multiple Cause of Death 2018\u20132022 on CDC WONDER Database. ."},{"key":"2024121402303576000_2024.12.11.627627v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.004"},{"key":"2024121402303576000_2024.12.11.627627v1.5","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01174"},{"key":"2024121402303576000_2024.12.11.627627v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.12.011"},{"key":"2024121402303576000_2024.12.11.627627v1.7","doi-asserted-by":"publisher","DOI":"10.1101\/gad.276304"},{"key":"2024121402303576000_2024.12.11.627627v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0724"},{"key":"2024121402303576000_2024.12.11.627627v1.9","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00033.2003"},{"key":"2024121402303576000_2024.12.11.627627v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccas.2022.06.011"},{"key":"2024121402303576000_2024.12.11.627627v1.11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063240"},{"key":"2024121402303576000_2024.12.11.627627v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2020.07.004"},{"key":"2024121402303576000_2024.12.11.627627v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.128"},{"key":"2024121402303576000_2024.12.11.627627v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-024-00544-7"},{"key":"2024121402303576000_2024.12.11.627627v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25329-5"},{"key":"2024121402303576000_2024.12.11.627627v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2024.01.003"},{"key":"2024121402303576000_2024.12.11.627627v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-00815-9"},{"key":"2024121402303576000_2024.12.11.627627v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.034"},{"key":"2024121402303576000_2024.12.11.627627v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43999-1"},{"key":"2024121402303576000_2024.12.11.627627v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.09.003"},{"key":"2024121402303576000_2024.12.11.627627v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.10.030"},{"key":"2024121402303576000_2024.12.11.627627v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.11.007"},{"key":"2024121402303576000_2024.12.11.627627v1.23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321769"},{"key":"2024121402303576000_2024.12.11.627627v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01526-4"},{"key":"2024121402303576000_2024.12.11.627627v1.25","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad841"},{"key":"2024121402303576000_2024.12.11.627627v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2797-4"},{"key":"2024121402303576000_2024.12.11.627627v1.27","doi-asserted-by":"publisher","DOI":"10.1101\/2024.11.13.623051"},{"key":"2024121402303576000_2024.12.11.627627v1.28","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120417-031559"},{"key":"2024121402303576000_2024.12.11.627627v1.29","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.60.1.267"},{"key":"2024121402303576000_2024.12.11.627627v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2012.04.005"},{"key":"2024121402303576000_2024.12.11.627627v1.31","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd8080089"},{"key":"2024121402303576000_2024.12.11.627627v1.32","doi-asserted-by":"publisher","DOI":"10.1126\/science.6844926"},{"key":"2024121402303576000_2024.12.11.627627v1.33","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036715"},{"key":"2024121402303576000_2024.12.11.627627v1.34","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.8860"},{"key":"2024121402303576000_2024.12.11.627627v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.02.011"},{"key":"2024121402303576000_2024.12.11.627627v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2015.04.004"},{"key":"2024121402303576000_2024.12.11.627627v1.37","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.145"},{"key":"2024121402303576000_2024.12.11.627627v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2011.09.004"},{"key":"2024121402303576000_2024.12.11.627627v1.39","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420470609"},{"key":"2024121402303576000_2024.12.11.627627v1.40","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20643"},{"key":"2024121402303576000_2024.12.11.627627v1.41","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12849"},{"key":"2024121402303576000_2024.12.11.627627v1.42","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13321"},{"key":"2024121402303576000_2024.12.11.627627v1.43","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13161"},{"key":"2024121402303576000_2024.12.11.627627v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.08.008"},{"key":"2024121402303576000_2024.12.11.627627v1.45","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.16.3061"},{"key":"2024121402303576000_2024.12.11.627627v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.12.015"},{"key":"2024121402303576000_2024.12.11.627627v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.06.028"},{"key":"2024121402303576000_2024.12.11.627627v1.48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62873"},{"key":"2024121402303576000_2024.12.11.627627v1.49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003405"},{"key":"2024121402303576000_2024.12.11.627627v1.50","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200068"},{"key":"2024121402303576000_2024.12.11.627627v1.51","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.29.591736"},{"key":"2024121402303576000_2024.12.11.627627v1.52","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.27.591127"},{"key":"2024121402303576000_2024.12.11.627627v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06311-1"},{"key":"2024121402303576000_2024.12.11.627627v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.10.014"},{"key":"2024121402303576000_2024.12.11.627627v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07171-z"},{"key":"2024121402303576000_2024.12.11.627627v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.079"},{"key":"2024121402303576000_2024.12.11.627627v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.025"},{"key":"2024121402303576000_2024.12.11.627627v1.58","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.89988"},{"key":"2024121402303576000_2024.12.11.627627v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0077-x"},{"key":"2024121402303576000_2024.12.11.627627v1.60","doi-asserted-by":"publisher","DOI":"10.4161\/cam.4.4.13489"},{"key":"2024121402303576000_2024.12.11.627627v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.04.005"},{"key":"2024121402303576000_2024.12.11.627627v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37015-9"},{"key":"2024121402303576000_2024.12.11.627627v1.63","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202152389"},{"key":"2024121402303576000_2024.12.11.627627v1.64","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2008.39"},{"key":"2024121402303576000_2024.12.11.627627v1.65","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-009-8076-x"},{"key":"2024121402303576000_2024.12.11.627627v1.66","doi-asserted-by":"publisher","DOI":"10.1126\/science.aas9536"},{"key":"2024121402303576000_2024.12.11.627627v1.67","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.184"},{"key":"2024121402303576000_2024.12.11.627627v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90018-3"},{"key":"2024121402303576000_2024.12.11.627627v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/990040"},{"key":"2024121402303576000_2024.12.11.627627v1.70","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-021-00499-5"},{"key":"2024121402303576000_2024.12.11.627627v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00693-z"},{"key":"2024121402303576000_2024.12.11.627627v1.72","doi-asserted-by":"publisher","DOI":"10.1242\/dev.079970"},{"key":"2024121402303576000_2024.12.11.627627v1.73","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8801"},{"key":"2024121402303576000_2024.12.11.627627v1.74","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.10.1043"},{"key":"2024121402303576000_2024.12.11.627627v1.75","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a037184"},{"key":"2024121402303576000_2024.12.11.627627v1.76","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0068"},{"key":"2024121402303576000_2024.12.11.627627v1.77","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.98"},{"key":"2024121402303576000_2024.12.11.627627v1.78","doi-asserted-by":"publisher","DOI":"10.1242\/dev.191320"},{"key":"2024121402303576000_2024.12.11.627627v1.79","doi-asserted-by":"publisher","DOI":"10.1101\/2023.04.05.535627"},{"key":"2024121402303576000_2024.12.11.627627v1.80","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208690109"},{"key":"2024121402303576000_2024.12.11.627627v1.81","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21054"},{"key":"2024121402303576000_2024.12.11.627627v1.82","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1077788"},{"key":"2024121402303576000_2024.12.11.627627v1.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.04.030"},{"key":"2024121402303576000_2024.12.11.627627v1.84","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-019-0365-z"},{"key":"2024121402303576000_2024.12.11.627627v1.85","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22762"},{"key":"2024121402303576000_2024.12.11.627627v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.092"},{"key":"2024121402303576000_2024.12.11.627627v1.87","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd3030028"},{"key":"2024121402303576000_2024.12.11.627627v1.88","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-11-137"},{"key":"2024121402303576000_2024.12.11.627627v1.89","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.04.013"},{"key":"2024121402303576000_2024.12.11.627627v1.90","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3775-16.2017"},{"key":"2024121402303576000_2024.12.11.627627v1.91","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-022-03629-6"},{"key":"2024121402303576000_2024.12.11.627627v1.92","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-20343-z"},{"key":"2024121402303576000_2024.12.11.627627v1.93","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.12.016"},{"key":"2024121402303576000_2024.12.11.627627v1.94","doi-asserted-by":"publisher","DOI":"10.1038\/nature11059"},{"key":"2024121402303576000_2024.12.11.627627v1.95","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(83)90100-8"},{"key":"2024121402303576000_2024.12.11.627627v1.96","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd7040054"},{"key":"2024121402303576000_2024.12.11.627627v1.97","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2007.00833.x"},{"key":"2024121402303576000_2024.12.11.627627v1.98","doi-asserted-by":"publisher","DOI":"10.1038\/20700"},{"key":"2024121402303576000_2024.12.11.627627v1.99","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118916"},{"key":"2024121402303576000_2024.12.11.627627v1.100","doi-asserted-by":"publisher","DOI":"10.3390\/biology13020105"},{"key":"2024121402303576000_2024.12.11.627627v1.101","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.11.012"},{"key":"2024121402303576000_2024.12.11.627627v1.102","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.733138"},{"key":"2024121402303576000_2024.12.11.627627v1.103","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0025-12.2012"},{"key":"2024121402303576000_2024.12.11.627627v1.104","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2023.0095"},{"key":"2024121402303576000_2024.12.11.627627v1.105","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260742"},{"key":"2024121402303576000_2024.12.11.627627v1.106","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-00686-0"},{"key":"2024121402303576000_2024.12.11.627627v1.107","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.10.006"},{"key":"2024121402303576000_2024.12.11.627627v1.108","doi-asserted-by":"publisher","DOI":"10.4161\/org.24892"},{"key":"2024121402303576000_2024.12.11.627627v1.109","doi-asserted-by":"publisher","DOI":"10.1038\/nature12354"},{"key":"2024121402303576000_2024.12.11.627627v1.110","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001444"},{"key":"2024121402303576000_2024.12.11.627627v1.111","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1746"},{"key":"2024121402303576000_2024.12.11.627627v1.112","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2006.12.004"},{"key":"2024121402303576000_2024.12.11.627627v1.113","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.05.037"},{"key":"2024121402303576000_2024.12.11.627627v1.114","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314789"},{"key":"2024121402303576000_2024.12.11.627627v1.115","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2022.03.012"},{"key":"2024121402303576000_2024.12.11.627627v1.116","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21719"},{"key":"2024121402303576000_2024.12.11.627627v1.117","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065143"},{"key":"2024121402303576000_2024.12.11.627627v1.118","doi-asserted-by":"publisher","DOI":"10.1242\/dev.173047"},{"key":"2024121402303576000_2024.12.11.627627v1.119","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10272"},{"key":"2024121402303576000_2024.12.11.627627v1.120","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.08.044"},{"key":"2024121402303576000_2024.12.11.627627v1.121","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2015.07.012"},{"key":"2024121402303576000_2024.12.11.627627v1.122","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.091208"},{"key":"2024121402303576000_2024.12.11.627627v1.123","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(16)34177-9"},{"key":"2024121402303576000_2024.12.11.627627v1.124","doi-asserted-by":"publisher","DOI":"10.2174\/156720110790396508"},{"key":"2024121402303576000_2024.12.11.627627v1.125","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.01.034"},{"key":"2024121402303576000_2024.12.11.627627v1.126","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.4673"},{"key":"2024121402303576000_2024.12.11.627627v1.127","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.2333"},{"key":"2024121402303576000_2024.12.11.627627v1.128","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2012-001148"},{"key":"2024121402303576000_2024.12.11.627627v1.129","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-018-1193-5"},{"key":"2024121402303576000_2024.12.11.627627v1.130","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312828"},{"key":"2024121402303576000_2024.12.11.627627v1.131","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2022.114756"},{"key":"2024121402303576000_2024.12.11.627627v1.132","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(15)30965-8"},{"key":"2024121402303576000_2024.12.11.627627v1.133","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000166755.29277.C4"},{"key":"2024121402303576000_2024.12.11.627627v1.134","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00165"},{"key":"2024121402303576000_2024.12.11.627627v1.135","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2021.106041"},{"key":"2024121402303576000_2024.12.11.627627v1.136","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01718-7"},{"key":"2024121402303576000_2024.12.11.627627v1.137","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03346-4"},{"key":"2024121402303576000_2024.12.11.627627v1.138","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.16.3071"},{"key":"2024121402303576000_2024.12.11.627627v1.139","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06964-9"},{"key":"2024121402303576000_2024.12.11.627627v1.140","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.26.564204"},{"key":"2024121402303576000_2024.12.11.627627v1.141","doi-asserted-by":"publisher","DOI":"10.1101\/2023.03.14.532676"},{"key":"2024121402303576000_2024.12.11.627627v1.142","doi-asserted-by":"publisher","DOI":"10.1101\/2022.08.01.502391"},{"key":"2024121402303576000_2024.12.11.627627v1.143","doi-asserted-by":"publisher","DOI":"10.1101\/2022.06.23.497419"},{"key":"2024121402303576000_2024.12.11.627627v1.144","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102713"},{"key":"2024121402303576000_2024.12.11.627627v1.145","doi-asserted-by":"publisher","DOI":"10.1101\/2023.08.18.552653"},{"key":"2024121402303576000_2024.12.11.627627v1.146","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3894397\/v1"},{"key":"2024121402303576000_2024.12.11.627627v1.147","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4233"},{"key":"2024121402303576000_2024.12.11.627627v1.148","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.03.012"},{"key":"2024121402303576000_2024.12.11.627627v1.149","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.06.061"},{"key":"2024121402303576000_2024.12.11.627627v1.150","doi-asserted-by":"publisher","DOI":"10.1002\/0470868066.ch8"},{"key":"2024121402303576000_2024.12.11.627627v1.151","doi-asserted-by":"publisher","DOI":"10.1039\/c2ib20060k"},{"key":"2024121402303576000_2024.12.11.627627v1.152","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233764"},{"key":"2024121402303576000_2024.12.11.627627v1.153","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00546.2020"},{"key":"2024121402303576000_2024.12.11.627627v1.154","doi-asserted-by":"publisher","DOI":"10.1113\/JP282828"},{"key":"2024121402303576000_2024.12.11.627627v1.155","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66303-3"},{"key":"2024121402303576000_2024.12.11.627627v1.156","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.05.002"},{"key":"2024121402303576000_2024.12.11.627627v1.157","doi-asserted-by":"publisher","DOI":"10.1109\/EMBC.2013.6610376"},{"key":"2024121402303576000_2024.12.11.627627v1.158","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063148"},{"key":"2024121402303576000_2024.12.11.627627v1.159","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000227505.19472.69"},{"key":"2024121402303576000_2024.12.11.627627v1.160","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01017.2006"},{"key":"2024121402303576000_2024.12.11.627627v1.161","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.935270"},{"key":"2024121402303576000_2024.12.11.627627v1.162","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00996-09"},{"key":"2024121402303576000_2024.12.11.627627v1.163","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.78.s1.04"},{"key":"2024121402303576000_2024.12.11.627627v1.164","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq391"},{"key":"2024121402303576000_2024.12.11.627627v1.165","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47929"},{"key":"2024121402303576000_2024.12.11.627627v1.166","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2015.06.002"},{"key":"2024121402303576000_2024.12.11.627627v1.167","doi-asserted-by":"publisher","DOI":"10.1101\/2024.11.06.622355"},{"key":"2024121402303576000_2024.12.11.627627v1.168","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.02.001"},{"key":"2024121402303576000_2024.12.11.627627v1.169","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-76715-4_12"},{"key":"2024121402303576000_2024.12.11.627627v1.170","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav7770"},{"key":"2024121402303576000_2024.12.11.627627v1.171","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490410215"},{"key":"2024121402303576000_2024.12.11.627627v1.172","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.77.2.211"},{"key":"2024121402303576000_2024.12.11.627627v1.173","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44244"},{"key":"2024121402303576000_2024.12.11.627627v1.174","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.554667"},{"key":"2024121402303576000_2024.12.11.627627v1.175","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.9.1745"},{"key":"2024121402303576000_2024.12.11.627627v1.176","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7182"},{"key":"2024121402303576000_2024.12.11.627627v1.177","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00281-4"},{"key":"2024121402303576000_2024.12.11.627627v1.178","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.24.2973"},{"key":"2024121402303576000_2024.12.11.627627v1.179","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2003.10.002"},{"key":"2024121402303576000_2024.12.11.627627v1.180","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67872"},{"key":"2024121402303576000_2024.12.11.627627v1.181","doi-asserted-by":"publisher","DOI":"10.3791\/63097"},{"key":"2024121402303576000_2024.12.11.627627v1.182","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"2024121402303576000_2024.12.11.627627v1.183","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"2024121402303576000_2024.12.11.627627v1.184","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0414-6"},{"key":"2024121402303576000_2024.12.11.627627v1.185","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3"},{"key":"2024121402303576000_2024.12.11.627627v1.186","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-3562"},{"key":"2024121402303576000_2024.12.11.627627v1.187","doi-asserted-by":"publisher","DOI":"10.3791\/63097-v"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.12.11.627627","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:39:21Z","timestamp":1768462761000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.12.11.627627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,11]]},"references-count":187,"URL":"https:\/\/doi.org\/10.1101\/2024.12.11.627627","relation":{},"subject":[],"published":{"date-parts":[[2024,12,11]]},"subtype":"preprint"}}