Single-cell omics identifies inflammatory signaling as a trans-differentiation trigger in mouse embryos

Dev Cell. 2024 Mar 18:S1534-5807(24)00109-6. doi: 10.1016/j.devcel.2024.02.010. Online ahead of print.ABSTRACTTrans-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.PMID:38508181 | DOI:10.1016/j.devc...

Source: Developmental Cell - March 20, 2024 Category: Cytology Authors: Yifan Zhang Zhixin Kang Mengyao Liu Lu Wang Feng Liu Source Type: research