Cell Fate Acquisition in the Xenopus laevis Mucociliary Epithelium: Cell-Cell Communication Using scRNA-seq and LIANA

Sammanfattning

The mucociliary epithelium is vital for airway defence, and its development depends on coordinated cell fate specification and intercellular signaling. Although single-cell studies have described cell-state transitions during Xenopus laevis mucociliary epithelium development, stage-resolved ligand-receptor communication networks remain incompletely characterized. To characterize stage-wise cell-cell communication during Xenopus laevis mucociliary epithelium development using LIANA-based ligand-receptor inference, with focused analysis of NOTCH-associated interactions and selected signaling-associated genes. A published time-resolved Xenopus laevis mucociliary epithelium single-cell RNA-seq dataset was processed through Xenopus-to-human ortholog mapping to enable compatibility with human ligand-receptor resources. For each developmental stage, LIANA was used to infer candidate ligand-receptor interactions between cell populations defined by Phenograph clustering. NOTCH-associated interactions were extracted from LIANA outputs, and selected stage 22 ligand-receptor-associated genes were annotated using DGIdb to explore approved drug-gene associations. The analysis revealed dynamic remodeling of inferred communication networks across development. Early stages showed relatively restricted ligand-receptor interaction patterns, whereas stage 22 represented the main expansion point (6,543 inferred interactions). Later stages displayed more structured communication with increased extracellular matrix- and adhesion-related programs. NOTCH-associated interactions showed the strongest expansion at stage 22, while Midkine-associated interactions recurred across several developmental stages. DGIdb annotation identified approved drug associations for selected genes, but also showed the limitations of translating developmental ligand-receptor inference into direct drug-prioritization conclusions. The thesis provides a systems-level view of inferred intercellular communication remodeling during mucociliary epithelium development. The findings identify candidate signaling programs for future validation and show how developmental cell-cell communication analysis can be connected to pharmaceutical bioinformatics while remaining limited by transcriptomics-based inference and gene-focused drug annotation.