Trans-differentiation represents a direct lineage conversion; however, insufficient characterization of this process hinders its potential applications. Here, to explore a potential universal principal for trans-differentiation, we performed single-cell transcriptomic analysis of endothelial-to-hematopoietic transition (EHT), endothelial-to-mesenchymal transition, and epithelial-to-mesenchymal transition in mouse embryos. We applied three scoring indexes of entropies, cell-type signature transcription factor expression, and critical transition signals to show common features underpinning the fate plasticity of transition states. Cross-model comparison identified inflammatory-featured transition states and a common trigger role of interleukin-33 in promoting fate conversions. Multimodal profiling (integrative transcriptomic and chromatin accessibility analysis) demonstrated the inflammatory regulation of hematopoietic specification. Furthermore, multimodal omics and fate-mapping analyses showed that endothelium-specific Spi1, as an inflammatory effector, governs appropriate chromatin accessibility and transcriptional programs to safeguard EHT. Overall, our study employs single-cell omics to identify critical transition states/signals and the common trigger role of inflammatory signaling in developmental-stress-induced fate conversions.

转分化代表直接的谱系转换；然而，对该过程的表征不足阻碍了其潜在的应用。在这里，为了探索转分化的潜在普遍原理，我们对小鼠胚胎中的内皮到造血转化（EHT）、内皮到间质转化和上皮到间质转化进行了单细胞转录组分析。我们应用了熵、细胞类型特征转录因子表达和关键过渡信号这三个评分指标来显示支撑过渡态命运可塑性的共同特征。跨模型比较确定了炎症特征的过渡状态和白细胞介素 33 在促进命运转变中的常见触发作用。多模式分析（综合转录组学和染色质可及性分析）证明了造血规范的炎症调节。此外，多模式组学和命运图谱分析表明，内皮特异性 Spi1 作为炎症效应子，控制适当的染色质可及性和转录程序以保护 EHT。总体而言，我们的研究采用单细胞组学来识别关键的过渡状态/信号以及炎症信号在发育应激诱导的命运转换中的常见触发作用。