{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:59:08Z","timestamp":1781632748455,"version":"3.54.5"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/50889-7, 2013\/17368-0, 2015\/50216-5"],"award-info":[{"award-number":["2014\/50889-7, 2013\/17368-0, 2015\/50216-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/05829-4"],"award-info":[{"award-number":["2017\/05829-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/14876-1; 2023\/05709-0"],"award-info":[{"award-number":["2021\/14876-1; 2023\/05709-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["465586\/2014-7; 309179\/2013-0; 442643\/2020-9"],"award-info":[{"award-number":["465586\/2014-7; 309179\/2013-0; 442643\/2020-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Generating mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) remains a major obstacle to accurate disease modeling and cardiac repair. As the transcription factor Irx3 is a key determinant of ventricular conduction system fate in mice, we hypothesized that suppressing\n                    <jats:italic>IRX3<\/jats:italic>\n                    expression accelerates human working cardiomyocyte differentiation. Here, we demonstrate that depleting\n                    <jats:italic>IRX3<\/jats:italic>\n                    enhances hiPSC-CM differentiation.\n                    <jats:italic>IRX3<\/jats:italic>\n                    -knockout (KO) hiPSCs generated a greater number of cardiomyocytes with elevated expression of TNNI1 and CX43. Notably,\n                    <jats:italic>IRX3<\/jats:italic>\n                    -KO cardiomyocytes exhibited improved electrophysiological properties, more uniform mitochondrial distribution, better sarcomere organization, and enhanced intercellular connectivity. We observed that\n                    <jats:italic>IRX3<\/jats:italic>\n                    expression peaks during the early stages of cardiomyocyte differentiation, whereas\n                    <jats:italic>IRX3<\/jats:italic>\n                    -KO cardiac progenitors have increased expression of GATA4, NKX2\u20135, and\n                    <jats:italic>TBX5<\/jats:italic>\n                    , as well as enhanced cell proliferation. These integrative analyses indicate that IRX3 influences cardiomyocyte differentiation by modulating the gene regulatory networks driven by GATA4, NKX2\u20135, and TBX5, providing functional evidence linking gene regulatory networks to the structural and electrophysiological development of cardiomyocytes. Collectively, these findings identify IRX3 as a key regulator of early cardiac commitment and highlight the potential of IRX3 suppression to enhance the molecular and functional phenotype of hiPSC-derived cardiomyocytes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0351704","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:33:57Z","timestamp":1781631237000},"page":"e0351704","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["IRX3 depletion promotes early cardiac commitment of hiPSC-Derived Cardiomyocytes"],"prefix":"10.1371","volume":"21","author":[{"given":"Agatha","family":"Ribeiro Kalthof","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas Dresch","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio 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