Abstract：
During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung\'s disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.
摘要：
在肠神经系统（ENS）发育过程中，开创性的波前肠神经c细胞（ENCC）启动肠道定植。然而,指导其规范和生态位相互作用的分子机制尚未完全了解。我们使用单细胞RNA测序和空间转录组学来绘制小鼠胚胎中波前ENCC的时空动力学和分子景观。我们的分析表明，在迁移过程中，波前ENCC效力逐渐下降，并确定了控制其规格和分化的转录因子。我们进一步描述了关键的信号通路(ephrin-Eph，Wnt-Frizzled,和Sema3a-Nrp1）被波前ENCC用于与周围细胞相互作用。这些途径的中断在人类Hirschsprung疾病的肠道组织中观察到，将它们与ENS畸形联系起来。此外,我们观察到区域特异性和细胞类型特异性的转录变化在周围的肠组织波阵面ENCC到达，表明它们在塑造肠道微环境中的作用。这项工作提供了ENS开发的路线图，对理解ENS疾病具有重要意义。
