Abstract
The dynamic and meticulously regulated networks established the foundation for embryonic development, where the intercellular interactions and signal transduction assumed a pivotal role. In recent years, high-throughput technologies such as single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have advanced dramatically, empowering the systematic dissection of cell-to-cell regulatory networks. The emergence of comprehensive databases and analytical frameworks has further provided unprecedented insights into embryonic development and cell-cell interactions (CCIs). This paper reviewed the exponential increased CCIs works related to developmental biology from 2008 to 2023, comprehensively collected and categorized 93 analytical tools and 39 databases, and demonstrated its practical utility through illustrative case studies. In parallel, the article critically scrutinized the persistent challenges within this field, such as the intricacies of spatial localization and transmembrane state validation at single-cell resolution, and underscored the interpretative limitations inherent in current analytical frameworks. The development of CCIs' analysis tools with harmonizing multi-omics data and the construction of cross-species dynamically updated CCIs databases will be the main direction of future research. Future investigations into CCIs are poised to expeditiously drive the application and clinical translation within developmental biology, unlocking novel dimensions for exploration and progress.