Enteric neural crest-derived cells at the invasive wavefront are transcriptionally distinct

Enteric nervous system (ENS) development relies on intestinal colonization by enteric neural crest-derived cells (ENCDCs). This is driven by a population of highly migratory and proliferative cells at the wavefront, but the unique molecular characteristics of the wavefront are unknown. ENCDCs from the wavefront and the trailing region proximal were isolated from 11.5 days post coitum (dpc) Wnt1-tdT mouse intestine and subjected to RNA-seq. Wavefront ENCDCs were transcriptionally distinct from trailing ENCDCs, and temporal modelling confirmed their relative immaturity. Wavefront ENCDCs exhibited altered expression of ECM and cytoskeletal genes, consistent with a migratory phenotype. Unlike postnatal enteric neural stem cells, wavefront ENCDCs possessed characteristics of cells undergoing epithelial-mesenchymal transition and lacked neuronal or glial commitment. Examination of mRNA profiles in enteric neural crest-derived cells at the invasive wavefront and trailing 1-1.5mm behind the wavefront.肠神经系统（Enteric Nervous System, ENS）的发育依赖于肠神经嵴来源细胞（enteric neural crest-derived cells, ENCDCs）的肠道定植。该过程由位于侵袭前沿的高度迁移、增殖细胞群体驱动，但目前学界对该前沿区域的独特分子特征尚不明确。研究人员从妊娠后天11.5天（days post coitum, dpc）的Wnt1-tdT小鼠肠道中，分离得到前沿区域与近端尾随区域的ENCDCs，并进行RNA测序（RNA-seq）分析。结果显示，前沿区域ENCDCs的转录特征与尾随区域存在显著差异，时序建模验证了前者相对未成熟的表型。前沿ENCDCs表现出细胞外基质与细胞骨架相关基因的表达异常，这与其迁移表型高度吻合。与出生后肠神经干细胞不同，前沿ENCDCs呈现上皮间质转化（epithelial-mesenchymal transition, EMT）的细胞特征，且未发生神经元或胶质细胞系的定向分化。本研究对侵袭前沿及前沿后方1-1.5mm的尾随区域ENCDCs的mRNA表达谱进行了检测分析。