Single-cell sequencing and organoids: applications in organ development and disease

The integration of single-cell sequencing and organoid technologies has been transformative for biomedical research, enabling investigations of organ development, disease mechanisms, and therapeutic innovation at even finer resolutions. Organoids serve as 3D in vitro models that replicate the structural and functional complexity of human tissues, while single-cell sequencing can resolve cellular heterogeneity, transcriptional dynamics, and lineage trajectories at high resolution. This review systematically explores the synergistic potential of these two technologies across multiple domains. First, it describes their application in studying the developmental mechanisms of organs including the brain, lungs, heart, liver, intestines, and kidneys, revealing key signaling pathways and cellular interaction networks. Then, it details their application in studying in vitro models of various diseases, including neurodegenerative disorders, genetic diseases, infectious diseases, metabolic syndrome, and tumors, advancing the in-depth analysis of pathological mechanisms. By leveraging patient-derived organoid biobanks, combining these two technologies can accelerate drug screening and precision, while utilizing transplantable tissue constructs to pioneer regenerative medicine strategies. This review also highlights the strengths of combining these two technologies in dynamically decoding cellular behavior and communication networks. By constructing physiologically relevant multifunctional research platforms, the integration of single-cell sequencing with organoid models will accelerate the elucidation of disease mechanisms and drive innovative breakthroughs in precision medicine and regenerative medicine. Looking ahead, the deep integration of single-cell sequencing with organoids, combined with cutting-edge technologies such as spatial transcriptomics and gene editing, will continue to propel life sciences toward a transformative leap from descriptive research to mechanism-driven, precision-oriented, and personalized approaches.