The Value of Single-cell Technologies in Solid Organ Transplantation Studies

Single-cell technologies open up new opportunities to explore the behavior of cells at the individual level. For solid organ transplantation, single-cell technologies can provide in-depth insights into the underlying mechanisms of the immunological processes involved in alloimmune responses after transplantation by investigating the role of individual cells in tolerance and rejection. Here, we review the value of single-cell technologies, including cytometry by time-of-flight and single-cell RNA sequencing, in the context of solid organ transplantation research. Various applications of single-cell technologies are addressed, such as the characterization and identification of immune cell subsets involved in rejection or tolerance. In addition, we explore the opportunities for analyzing specific alloreactive T- or B-cell clones by linking phenotype data to T- or B-cell receptor data, and for distinguishing donor- from recipient-derived immune cells. Moreover, we discuss the use of single-cell technologies in biomarker identification and risk stratification, as well as the remaining challenges. Together, this review highlights that single-cell approaches contribute to a better understanding of underlying immunological mechanisms of rejection and tolerance, thereby potentially accelerating the development of new or improved therapies to avoid allograft rejection.