上皮向间充质转化（EMTs）通过内膜和外膜引导心房室边界瓣膜的形成，但组织的细胞复杂性和小尺度限制了分析。为了解决这些问题，我们分析了从胚胎第7.75天（E7.75）的心脏到第12.5天（E12.5）的心房室道的50,000多个小鼠单细胞转录组。我们描述了内膜EMT过程中的间充质和内膜分叉，识别了外膜EMT过程中的不同的转分化外膜人口，并揭示了上皮-间充质可塑性在两个过程中的激活。在Sox9缺陷瓣膜中，我们观察到上皮-间充质可塑性增加，表明SOX9在促进内皮和间充质细胞命运决策中起到了作用。最后，我们解析了引导心脏瓣膜EMTs启动和进展的细胞相互作用。总的来说，这些数据揭示了内膜或外膜向间充质转化的机制，并将作为EMT启动和进展的图谱，具有再生医学和癌症生物学的广泛影响。© 2023 Springer Nature Limited.

Epithelial-to-mesenchymal transitions (EMTs) of both endocardium and epicardium guide atrioventricular heart valve formation, but the cellular complexity and small scale of this tissue have restricted analyses. To circumvent these issues, we analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 hearts to E12.5 atrioventricular canals. We delineate mesenchymal and endocardial bifurcation during endocardial EMT, identify a distinct, transdifferentiating epicardial population during epicardial EMT, and reveal the activation of epithelial-mesenchymal plasticity during both processes. In Sox9-deficient valves, we observe increased epithelial-mesenchymal plasticity, indicating a role for SOX9 in promoting endothelial and mesenchymal cell fate decisions. Lastly, we deconvolve cell interactions guiding the initiation and progression of cardiac valve EMTs. Overall, these data reveal mechanisms of emergence of mesenchyme from endocardium or epicardium at single-cell resolution and will serve as an atlas of EMT initiation and progression with broad implications in regenerative medicine and cancer biology.© 2023. Springer Nature Limited.