Single-cell transcriptomic profiling of C. elegans Q neuroblast lineage during migration and differentiation

Proper migration and differentiation of neuroblasts into neurons are essential for the development of a healthy nervous system. In this context, the asymmetrical migration of Caenorhabditis elegans Q neuroblasts provides a powerful model for studying the genetic aspects of neuronal migration in vivo at single-cell resolution. We isolated Q lineage cells at various stages of development using FACS and employed single-cell RNA sequencing to investigate the molecular mechanisms underlying the migration and differentiation of these neuroblasts. We created a robust transcriptomic differentiation map of the Q neuroblast lineage and used established markers to identify each cell in the lineage. Our results revealed novel genes not previously described on these cells and linked the expression of known genes to specific stages of Q lineage progression. Furthermore, functional enrichment and imaging provided evidence that the parent Q cells are initially specified with an epithelial-like identity and undergo epithelial-mesenchymal transition during the early stages of migration. We also identified novel Wnt-related mechanisms, including left-right asymmetric expression of cwn-1 and cwn-2, and the involvement of the Wnt/β-catenin asymmetry pathway in the Q lineage. Our work offers a high-resolution view of neuroblast development, showcasing the power of single-cell transcriptomics to reveal stagespecific regulatory programs.