Guoyang Zhang, Weixuan Lin, Lin Guo, Ziyun Li, Yu Xiang, Luo Wang, Xiaoyu Yan
A clear mechanistic understanding of the skeletal system's physiological and pathological processes is essential for therapeutic research. Traditional bulk analysis methods cannot resolve cellular heterogeneity and dynamic intercellular signaling in bone microenvironments, limiting insights into skeletal biology. This review focuses on the hierarchical application of single-cell technologies: transcriptomics for cellular identity, spatial omics for tissue context, and multi-omics integration for holistic exploration. These technologies resolve undetectable cellular heterogeneity, identify key cell subpopulations and intercellular communication pathways, and illuminate mechanistic insights. We synthesize their applications, address implementation challenges, and highlight their potential to guide future skeletal research and treatment.