期刊论文详细信息
Frontiers in Immunology
Advanced Genomics-Based Approaches for Defining Allograft Rejection With Single Cell Resolution
Brian M. Baker1  Krishna Roskin3  E. Steve Woodle5  David Hildeman6  Tiffany Shi7 
[1] Department of Chemistry and Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, United States;Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States;Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States;Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States;
关键词: transplantation;    allograft rejection;    genomics;    sequencing;    single cell RNA seq;   
DOI  :  10.3389/fimmu.2021.750754
来源: DOAJ
【 摘 要 】

Solid organ transplant recipients require long-term immunosuppression for prevention of rejection. Calcineurin inhibitor (CNI)-based immunosuppressive regimens have remained the primary means for immunosuppression for four decades now, yet little is known about their effects on graft resident and infiltrating immune cell populations. Similarly, the understanding of rejection biology under specific types of immunosuppression remains to be defined. Furthermore, development of innovative, rationally designed targeted therapeutics for mitigating or preventing rejection requires a fundamental understanding of the immunobiology that underlies the rejection process. The established use of microarray technologies in transplantation has provided great insight into gene transcripts associated with allograft rejection but does not characterize rejection on a single cell level. Therefore, the development of novel genomics tools, such as single cell sequencing techniques, combined with powerful bioinformatics approaches, has enabled characterization of immune processes at the single cell level. This can provide profound insights into the rejection process, including identification of resident and infiltrating cell transcriptomes, cell-cell interactions, and T cell receptor α/β repertoires. In this review, we discuss genomic analysis techniques, including microarray, bulk RNAseq (bulkSeq), single-cell RNAseq (scRNAseq), and spatial transcriptomic (ST) techniques, including considerations of their benefits and limitations. Further, other techniques, such as chromatin analysis via assay for transposase-accessible chromatin sequencing (ATACseq), bioinformatic regulatory network analyses, and protein-based approaches are also examined. Application of these tools will play a crucial role in redefining transplant rejection with single cell resolution and likely aid in the development of future immunomodulatory therapies in solid organ transplantation.

【 授权许可】

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