Comparative Single-Cell Transcriptome Analysis of Early Innate Lymphoid Cell Development in Humans and Mice

Background and Objective: Innate lymphoid cells (ILCs) are key immune cells involved in immune balance, pathogen defense, and tissue repair. However, their development, particularly in humans, is not well understood. This study maps ILC development in the mouse fetal liver and compares it with human ILC development, focusing on species-specific differences. Materials and Methods: This study compares ILC development between humans and mice to identify species-specific differences. Single-cell RNA sequencing data from human fetal tissues were obtained from GEO (GSE163587), while adult mouse bone marrow data (GSE113767) were used to identify ILC progenitors, including ALP, sEILP, cEILP, ILCP, and ILC2P. Homologous gene pairs between species were found using the bioMart package in R. Canonical correlation analysis (CCA) integrated the datasets, followed by PCA and UMAP for dimensionality reduction. Differential gene expression and functional enrichment were analyzed with DESeq2 and cluster Profiler. Pseudotime analysis using Monocle2 was used to infer the developmental trajectories of ILC populations in both species. Results: Current findings indicate the presence of an ILC developmental pathway in the mouse fetal liver that shares similarities with that in the bone marrow, demonstrating even more pronounced cellular proliferation in the fetal liver. The comparison between humans and mice revealed both conserved and divergent aspects of ILC development at cellular and molecular levels, including the regulation of key transcription factors and specific molecular expression patterns. Notably, this study uncovered distinct ILC subtypes specific to the embryonic stage in humans, which are postulated to play significant roles in the immune ecology of various tissues and organs. Conclusion: These discoveries enhance our understanding of ILC developmental processes and provide valuable theoretical support and practical guidance for research on the in vitro regeneration and application of ILCs.