The T-box family transcription factor 18 (Tbx18) has been found to play a critical role in regulating the development of the mammalian heart during the primary stages of embryonic development while the cellular heterogeneity and landscape of Tbx18-positive (Tbx18+) cardiac cells remain incompletely characterized. Here, we analyzed prior published single-cell RNA sequencing (scRNA-seq) mouse heart data to explore the heterogeneity of Tbx18+ cardiac cell subpopulations and provide a comprehensive transcriptional landscape of Tbx18+ cardiac cells during their development. Bioinformatic analysis methods were utilized to identify the heterogeneity between cell groups. Based on the gene expression characteristics, Tbx18+ cardiac cells can be classified into a minimum of two distinct cell populations, namely fibroblast-like cells and cardiomyocytes. In terms of temporal heterogeneity, these cells exhibit three developmental stages, namely the MEM stage, ML_P0 stage, and P stage Tbx18+ cardiac cells. Furthermore, Tbx18+ cardiac cells encompass several cell types, including cardiac progenitor-like cells, cardiomyocytes, and epicardial/stromal cells, as determined by specific transcriptional regulatory networks. The scRNA-seq results revealed the involvement of extracellular matrix (ECM) signals and epicardial epithelial-to-mesenchymal transition (EMT) in the development of Tbx18+ cardiac cells. The utilization of a lineage-tracing model served to validate the crucial function of Tbx18 in the differentiation of cardiac cells. Consequently, these findings offer a comprehensive depiction of the cellular heterogeneity within Tbx18+ cardiac cells.

人们发现 T-box 家族转录因子 18 (Tbx18) 在胚胎发育初级阶段调节哺乳动物心脏的发育中发挥着关键作用，同时 Tbx18 阳性 (Tbx18+) 心脏细胞的细胞异质性和景观仍然存在不完全表征。在这里，我们分析了先前发表的单细胞 RNA 测序 (scRNA-seq) 小鼠心脏数据，以探索 Tbx18+ 心脏细胞亚群的异质性，并提供 Tbx18+ 心脏细胞在发育过程中的全面转录情况。利用生物信息分析方法来识别细胞群之间的异质性。根据基因表达特征，Tbx18+心肌细胞可分为至少两个不同的细胞群，即成纤维细胞样细胞和心肌细胞。就时间异质性而言，这些细胞表现出三个发育阶段，即MEM阶段、ML_P0阶段和P阶段Tbx18+心肌细胞。此外，Tbx18+心脏细胞涵盖多种细胞类型，包括心脏祖细胞样细胞、心肌细胞和心外膜/基质细胞，由特定的转录调控网络决定。scRNA-seq结果揭示了细胞外基质（ECM）信号和心外膜上皮间质转化（EMT）参与Tbx18+心脏细胞的发育。利用谱系追踪模型验证了 Tbx18 在心肌细胞分化中的关键功能。因此，这些发现全面描述了 Tbx18+ 心肌细胞内的细胞异质性。