AcoResearch
Cross-Species Comparative Multi-omics Analysis Unveils the Neural Origin of Basal Metazoans
Introduction
Understanding the origin and early evolution of the nervous system is a central question in evolutionary developmental biology. Basal metazoans, including Placozoa and Cnidaria, occupy key phylogenetic positions spanning the transition from absence to presence of nervous systems. Using the moon jellyfish Aurelia coerulea as a model, this study integrates technological innovation, multi-omics atlas construction, cross-species comparison, and dynamic network analysis to investigate early neural evolution at molecular and cellular levels.
Methodology
We developed GSP-Cryo, a gelatin-assisted cryosectioning workflow optimized for fragile, water-rich jellyfish tissues, enabling high-quality spatial transcriptomics. A chromosome-level genome was assembled and refined using CycloneSeq long-read transcripts. Single-nucleus (snRNA-seq) and spatial (Stereo-seq) transcriptomics were integrated to build a comprehensive A. coerulea multi-omics atlas (AMOA). Cross-species analyses were performed across 9 basal species. Dynamic Network Biomarker analysis was applied to detect early-warning signals during neural origin transitions.
Results
The 554.10 Mb genome of A. coerulea was assembled using WGS, PacBio HiFi, Hi-C, and RNA-seq. CycloneSeq refinement improved gene models and annotation. Single-nucleus transcriptomics profiled 32,660 cells, revealing 7 major cell types and 2,318 DEGs. Spatial transcriptomics mapped 10,549 Stereo-seq spots, highlighting 4 key umbrella-margin cell types. Cross-species integration encompassed 173,786 cells from 9 basal species. Comparative analyses combining static multi-omics and dynamic network approaches identified 109 NCE-COGs, 154 NC-DEOGs, and 165 NO-DNBGs, revealing the progressive emergence of neural cell types and functional enrichment along evolution.
Conclusion
We established an integrated framework combining static and dynamic analyses to investigate early neural evolution. Static analyses included comparative genomics and cross-species single-cell transcriptomics, while dynamic analysis applied Dynamic Network Biomarker (DNB) modeling. Six candidate genes (CACNA2D3, LHX1, KCNA1, DUSP16, KCNK9, and TUBA1A) were prioritized as they simultaneously exhibit lineage-specific evolutionary signals, neural cell-type differential expression, and early-stage dynamic network warning properties, giving them higher integrative priority. These findings highlight the stepwise emergence of neural modules and cell specialization in basal metazoans.
Acknowledgements
We thank Prof. Luonan Chen (Shanghai Jiao Tong University) and Prof. Xun Xu (BGI Research) for their joint mentorship and guidance throughout this study.
