AUTHOR=Mou Lisha , Wang Tony Bowei , Chen Yuxian , Luo Ziqi , Wang Xinyu , Pu Zuhui TITLE=Single-cell genomics and spatial transcriptomics in islet transplantation for diabetes treatment: advancing towards personalized therapies JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1554876 DOI=10.3389/fimmu.2025.1554876 ISSN=1664-3224 ABSTRACT=Diabetes mellitus (DM) is a global health crisis affecting millions, with islet transplantation emerging as a promising treatment strategy to restore insulin production. This review synthesizes the current research on single-cell and spatial transcriptomics in the context of islet transplantation, highlighting their potential to revolutionize DM management. Single-cell RNA sequencing, offers a detailed look into the diversity and functionality within islet grafts, identifying specific cell types and states that influence graft acceptance and function. Spatial transcriptomics complements this by mapping gene expression within the tissue’s spatial context, crucial for understanding the microenvironment surrounding transplanted islets and their interactions with host tissues. The integration of these technologies offers a comprehensive view of cellular interactions and microenvironments, elucidating mechanisms underlying islet function, survival, and rejection. This understanding is instrumental in developing targeted therapies to enhance graft performance and patient outcomes. The review emphasizes the significance of these research avenues in informing clinical practices and improving outcomes for patients with DM through more effective islet transplantation strategies. Future research directions include the application of these technologies in personalized medicine, developmental biology, and regenerative medicine, with the potential to predict disease progression and treatment responses. Addressing ethical and technical challenges will be crucial for the successful implementation of these integrated approaches in research and clinical practice, ultimately enhancing our ability to manage DM and improve patient quality of life.