生物
转录组
转录因子
细胞生物学
染色质
细胞命运测定
过渡(遗传学)
上皮-间质转换
细胞分化
计算生物学
遗传学
基因表达
基因
作者
Yifan Zhang,Zhixin Kang,Mengyao Liu,Lu Wang,Feng Liu
标识
DOI:10.1016/j.devcel.2024.02.010
摘要
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.
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