*Purpose: Allograft rejection is still the leading causes of the graft loss, especially long-term outcome. Single-cell genomics techniques are revolutionizing our ability to comprehensively characterize the diversity of immune cell types and quantify subtle transcriptional differences between rare cell types in a transplanted organ undergoing rejection. We aim to report a map of the cellular landscape of cardiac allograft rejection using single-cell RNA sequencing.

*Methods: Here we characterized non-cardiac and cardiac cell from hearts in allogeneic and syngeneic mouse heart transplantation model to define an atlas of the major immune cell types and most native cardiac cell types during cardiac allograft rejection.

*Results: We acquire the transcriptomic atlas of 38602 individual non-cardiac and cardiac cell from allogeneic and syngeneic mouse heart transplantation. We identified 20 distinct cell clusters expressing known markers of major cell types, the clusters comprised endothelial cells, fibroblasts, granulocytes, cardiomyocyte, lymphocytes, pericytes, macrophages, dendritic cell (DC)-like cells, smooth muscle cells. Cell trajectory analysis revealed that components of multiple graft rejection-related pathways and transcription factors were differentially expressed along allogeneic heart graft. Our analyses also showed extensive networks of intercellular communication in gene expression in the allogeneic heart graft.

*Conclusions: These data unprecedentedly uncovered the transcriptional landscape and phenotypic heterogeneity of the major immune cell types and most native cardiac cell types and identified previously unrecognized rare cell types in graft rejection in the mouse heart transplantation. Applying this technology could lead to the discovery of new therapeutic targets relevant for allograft rejection.

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