RRC ID 85431
著者 Dong A, Yoshizumi M, Kokubo H.
タイトル Odz4 upregulates SAN-specific genes to promote differentiation into cardiac pacemaker-like cells.
ジャーナル FEBS Lett
Abstract 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-seq data and identified Odz4 as a SAN-specific candidate. In situ hybridization revealed Odz4 expression in the cardiac crescent and throughout the cardiac conduction system (CCS). To assess the role of Odz4 in CCS differentiation, we utilized a Tet-Off inducible system for its intracellular domain (ICD). Embryonic bodies (EBs) exogenously expressing Odz4-ICD exhibited an increased propensity to develop into pacemaker-like cells with enhanced automaticity and upregulated expression of SAN-specific genes. CellChat and GO analyses unveiled SAN-specific enrichment of ligand-receptor sets, especially Ptn-Ncl, and extracellular matrix components in the group exogenously expressing Odz4-ICD. Our findings underscore the significance of Odz4 in SAN development and offer fresh insights into biological pacemaker establishment.
巻・号 599(3)
ページ 299-315
公開日 2025-2-1
DOI 10.1002/1873-3468.15036
PMID 39462648
PMC PMC11808419
MeSH Animals Cell Differentiation* / genetics Humans Mice Myocytes, Cardiac* / cytology Myocytes, Cardiac* / metabolism Sick Sinus Syndrome / genetics Sick Sinus Syndrome / metabolism Sinoatrial Node* / cytology Sinoatrial Node* / metabolism Up-Regulation
IF 3.057
リソース情報
ヒト・動物細胞 COS-7(RCB0539) EBRTcH3(AES0054)