Dataset related to the article "Transcription regulation by TBX18 in smooth muscle cells is essential for normal aortic development and homeostasis"

This record contains raw data related to the article “Transcription regulation by TBX18 in smooth muscle cells is essential for normal aortic development and homeostasis”. ABSTRACT AimsThis study investigated whether TBX18, a transcription factor known for its critical roles in cardiovascular and urogenital development, but never previously studied in the context of the aorta, contributes to the normal development and homeostasis of this major artery. Methods and resultsHistological analyses revealed Tbx18 expression in smooth muscle cells (SMCs) of the adult and embryonic aorta. Following this observation, transgenic mouse models were used to promote ablation of Tbx18 in SMCs from early embryogenesis or in adulthood. Phenotypes were assessed by quantitative imaging and histological analyses. Embryonic conditional ablation of Tbx18 resulted in severe aortic malformations and lethality, whereas adult ablation resulted in milder phenotypes. However, when adult Tbx18 ablation was combined with a Marfan-causing mutation, it promoted exacerbated degradation of aortic ultrastructure, aortic root dilation and lethality. Multiomics analyses at the transcriptomic and translatomic levels revealed upregulation of immediate early genes (IEGs) encoding critical transcription factors such as EGR1, FOS and JUNB in SMCs from Marfan aortae, a response further exacerbated by concomitant ablation of Tbx18. ChIP-seq in primary human aortic SMCs revealed that TBX18 directly binds to several of the genes that were misexpressed in mutant aortae, suggesting direct regulation. Finally, transcriptomic and histological analyses of human patient samples revealed that TBX18 expression was downregulated in aneurysms, with the extent of downregulation correlating with lesion severity. ConclusionsThese results demonstrated that TBX18 in SMCs is essential not only for normal aortic development, but also for preventing gene expression programs linked to adverse remodeling in adulthood. These findings enhance our understanding of the function of this transcription factor and of molecular mechanisms underlying aneurysm formation, a pathology responsible for a significant number of fatalities in developed countries.本数据集包含与论文《平滑肌细胞中TBX18的转录调控对正常主动脉发育及稳态维持至关重要》相关的原始数据。 摘要 研究目的 本研究旨在探究在心血管与泌尿生殖系统发育中发挥关键作用的转录因子（transcription factor）TBX18——此前从未在主动脉相关研究中被探讨——是否参与该大动脉的正常发育与稳态维持。 方法与结果 组织学分析显示，成年及胚胎期主动脉的平滑肌细胞（smooth muscle cells, SMCs）中存在Tbx18的表达。基于这一发现，本研究使用转基因小鼠模型，在胚胎早期或成年阶段的平滑肌细胞中敲除Tbx18。通过定量成像与组织学分析评估表型。胚胎期条件性敲除Tbx18会导致严重的主动脉畸形与胚胎致死，而成年期敲除则引发较轻的表型。然而，当成年Tbx18敲除与马凡综合征致病突变结合时，会加剧主动脉超微结构的降解、主动脉根部扩张，并导致死亡。转录组（transcriptomic）与翻译组（translatomic）水平的多组学分析显示，马凡综合征主动脉的平滑肌细胞中，编码EGR1、FOS与JUNB等关键转录因子的即刻早期基因（immediate early genes, IEGs）表达上调，而同时敲除Tbx18会进一步增强这一应答反应。对原代人主动脉平滑肌细胞进行的染色质免疫沉淀测序（ChIP-seq）结果显示，TBX18可直接结合突变主动脉中异常表达的多个基因，提示其存在直接调控作用。最后，对人类患者样本的转录组与组织学分析显示，动脉瘤患者的主动脉中TBX18表达下调，且下调程度与病变严重程度呈正相关。 结论 本研究结果表明，平滑肌细胞中的TBX18不仅对主动脉的正常发育至关重要，还可在成年阶段阻止与不良重构相关的基因表达程序。这些发现加深了我们对该转录因子功能以及动脉瘤形成分子机制的理解，而动脉瘤是发达国家致死率居高不下的病理病症之一。