{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:54:56Z","timestamp":1772117696446,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T00:00:00Z","timestamp":1729987200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T00:00:00Z","timestamp":1729987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2132"],"award-info":[{"award-number":["JPMJSP2132"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K06791"],"award-info":[{"award-number":["22K06791"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    Cardiac arrhythmias stemming from abnormal sinoatrial node (SAN) function can lead to sudden death. Developing a biological pacemaker device for treating sick sinus syndrome (SSS) could offer a potential cure. Understanding SAN differentiation is crucial, yet its regulatory mechanism remains unclear. We reanalyzed published RNA\u2010seq data and identified\n                    <jats:italic>Odz4<\/jats:italic>\n                    as a SAN\u2010specific candidate.\n                    <jats:italic>In situ<\/jats:italic>\n                    hybridization revealed\n                    <jats:italic>Odz4<\/jats:italic>\n                    expression in the cardiac crescent and throughout the cardiac conduction system (CCS). To assess the role of\n                    <jats:italic>Odz4<\/jats:italic>\n                    in CCS differentiation, we utilized a Tet\u2010Off inducible system for its intracellular domain (ICD). Embryonic bodies (EBs) exogenously expressing\n                    <jats:italic>Odz4<\/jats:italic>\n                    \u2010\n                    <jats:italic>ICD<\/jats:italic>\n                    exhibited an increased propensity to develop into pacemaker\u2010like cells with enhanced automaticity and upregulated expression of SAN\u2010specific genes. CellChat and GO analyses unveiled SAN\u2010specific enrichment of ligand\u2013receptor sets, especially Ptn\u2010Ncl, and extracellular matrix components in the group exogenously expressing\n                    <jats:italic>Odz4\u2010ICD<\/jats:italic>\n                    . Our findings underscore the significance of\n                    <jats:italic>Odz4<\/jats:italic>\n                    in SAN development and offer fresh insights into biological pacemaker establishment.\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.15036","type":"journal-article","created":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T22:21:06Z","timestamp":1730067666000},"page":"299-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Odz4<\/i>\n                    upregulates\n                    <scp>SAN<\/scp>\n                    \u2010specific genes to promote differentiation into cardiac pacemaker\u2010like cells"],"prefix":"10.1002","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0076-8594","authenticated-orcid":false,"given":"Anqi","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Hiroshima University  Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masao","family":"Yoshizumi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Hiroshima University  Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kokubo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Hiroshima University  Japan"},{"name":"Department of Physical Therapy Tohto University  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(70)90580-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000258019.74591.b3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccep.2018.02.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1408897"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2011.120"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14664"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.05.023"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.416007"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.12.028"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0031-y"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.187062"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000227571.84189.65"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq033"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCEP.121.009957","article-title":"Implementing biological pacemakers: design criteria for successful","volume":"14","author":"Elizabeth RK","year":"2021","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110612"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27018"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.11.004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3745"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3106"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.07.014"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.145.3.563"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.11.038"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.034967"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-13-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29751-1"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2058"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65485-0"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2045-11.2012"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103063"},{"key":"e_1_2_9_31_1","first-page":"3339","article-title":"Genome\u2010wide association study reveals two new risk loci for bipolar disorder","volume":"24","author":"Thomas WM","year":"2014","journal-title":"Nat Commun"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.598064"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni043"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0185125","article-title":"Biochemical and biomechanical properties of the pacemaking sinoatrial node extracellular matrix are distinct from contractile left ventricular matrix","volume":"12","author":"Jessica MG","year":"2017","journal-title":"PLoS One"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10709-9"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305913"},{"key":"e_1_2_9_37_1","article-title":"Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program","volume":"146","author":"Vincent WW","year":"2019","journal-title":"Development"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314578"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2986"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07333-4"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.042"},{"key":"e_1_2_9_42_1","first-page":"45","article-title":"Increased mesodermal and mesendodermal populations by BMP4 treatment facilitates human iPSC line differentiation into a cardiac lineage","volume":"15","author":"Maya K","year":"2019","journal-title":"J Stem Cells Regen Med"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.050"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.208041"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00170"},{"key":"e_1_2_9_46_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.03726","article-title":"Synaptic organization of the drosophila antennal lobe and its regulation by the Teneurins","volume":"3","author":"Timothy JM","year":"2014","journal-title":"Elife"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22616"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113505"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.075"},{"key":"e_1_2_9_50_1","article-title":"Pleiotrophin as a central nervous system neuromodulator, evidences from the hippocampus","volume":"8","author":"Celia G","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2016.07.004"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.210122ep"}],"container-title":["FEBS Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.15036","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.15036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T06:42:40Z","timestamp":1764484960000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1873-3468.15036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,27]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/1873-3468.15036"],"URL":"https:\/\/doi.org\/10.1002\/1873-3468.15036","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/1873-3468.15036\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1873-3468.15036\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1873-3468.15036\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1873-3468.15036\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1873-3468.15036\/v2\/review1","asserted-by":"object"}]},"ISSN":["0014-5793","1873-3468"],"issn-type":[{"value":"0014-5793","type":"print"},{"value":"1873-3468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,27]]},"assertion":[{"value":"2024-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}