| First Author | Zhang Y | Year | 2024 |
| Journal | Dev Cell | Volume | 59 |
| Issue | 8 | Pages | 961-978.e7 |
| PubMed ID | 38508181 | Mgi Jnum | J:347666 |
| Mgi Id | MGI:7626203 | Doi | 10.1016/j.devcel.2024.02.010 |
| Citation | Zhang Y, et al. (2024) Single-cell omics identifies inflammatory signaling as a trans-differentiation trigger in mouse embryos. Dev Cell 59(8):961-978.e7 |
| abstractText | 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. |
