Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China.
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
Dev Cell. 2024 Apr 22;59(8):961-978.e7. doi: 10.1016/j.devcel.2024.02.010. Epub 2024 Mar 19.
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.
转分化代表一种直接的谱系转换；然而，由于对这一过程的特征描述不足，限制了其潜在的应用。在这里，为了探索转分化的潜在通用原理，我们对小鼠胚胎中的内皮细胞向造血细胞转化（EHT）、内皮细胞向间充质细胞转化和上皮细胞向间充质细胞转化进行了单细胞转录组分析。我们应用了三种熵评分指标、细胞类型特征转录因子表达和关键转化信号，以显示转化状态下命运可塑性的共同特征。跨模型比较确定了具有炎症特征的转化状态，以及白细胞介素-33在促进命运转化中的共同触发作用。多模态分析（整合转录组和染色质可及性分析）表明了造血特化的炎症调控。此外，多模态组学和命运映射分析表明，内皮细胞特异性 Spi1 作为一种炎症效应因子，控制适当的染色质可及性和转录程序，以保障 EHT。总的来说，我们的研究利用单细胞组学来鉴定关键的转化状态/信号，以及炎症信号在发育应激诱导的命运转化中的共同触发作用。
