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Technical advancements in single-cell genomics have improved our understanding of molecular and genetic regulation. All cell types in the human body can now be characterized using single-cell multi-omics analyses, which help uncover the complex genetic and epigenetic regulatory mechanisms and indicate cellular interactions within tissues. Now, as single-cell research moves toward clinical implementation, it is being incorporated in diagnostic and therapeutic measures for precision medicine. This special issue in single-cell genomics provides a comprehensive view of the current technological status and the future perspectives and applications of single-cell analysis.