Abstract:
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.
摘要:
跨分化代表直接的谱系转换;然而,该过程的描述不足阻碍了其潜在的应用。这里,为了探索跨分化的潜在普遍原则,我们进行了内皮细胞到造血转换(EHT)的单细胞转录组学分析,内皮-间质转化,和小鼠胚胎中的上皮-间质转化。我们应用了熵的三个评分指标,细胞型特征转录因子表达,和关键过渡信号,以显示共同特征,支撑过渡态的命运可塑性。跨模型比较确定了炎症特征的过渡状态和白细胞介素-33在促进命运转换中的常见触发作用。多模态分析(整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作为一种炎症效应物,管理适当的染色质可及性和转录程序以保护EHT。总的来说,我们的研究使用单细胞组学来鉴定关键过渡态/信号,以及炎症信号在发育应激诱导的命运转换中的共同触发作用.