Advanced omics approaches in liver transplant settings: current applications and future prospectives

Abstract

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), as advanced omics technologies, have addressed critical challenges in liver transplantation (LT), the most effective treatment for end-stage liver disease. This review aims to summarize the applications and future directions of scRNA-seq and ST in the context of LT. We highlight their role in uncovering immune cell heterogeneity and related injury mechanisms post-transplantation. From a clinician's perspective, we also outline potential future developments in the application of advanced omics in LT. Specifically, we focus on key immune cells involved in LT, with an emphasis on post-transplant immune responses and ischemia-reperfusion injury (IRI), as revealed by scRNA-seq and ST. Furthermore, we underscore the importance of multi-omics approaches and dynamic omics analyses in clinical LT research. With ongoing technological advancements, the integration of cutting-edge omics technologies and artificial intelligence (AI) holds great promise for advancing precision medicine in LT. Emphasis should be placed on the value of single-cell and spatial omics technologies in improving precision therapy and clinical management for LT patients.

Keywords: cell heterogeneity; liver transplantation; precision medicine; single-cell sequencing; spatial transcriptomics.

Figure 1

Role of various immune molecules in liver transplantation immune tolerance. APC, antigen-presenting cell; CTLA-4, Cytotoxic T-lymphocyte-associated protein 4; DC, dendritic cell; Fas, Factor associated suicide; FasL, Factor associated suicide ligandHLA-G, Human leukocyte antigen G; HLA-I, Human leukocyte antigen I.

Figure 2

Related cells and molecules that influence liver transplantation rejection. APOE, Apolipoprotein E; CTL, Cytotoxic T cell; CTLA-4, Cytotoxic T-lymphocyte-associated protein 4; DC, dendritic cell; IRI, ischemia-reperfusion injury; FLT3, Fms-like tyrosine kinase 3; FOS, Fos Proto-Oncogene, AP-1 Transcription Factor Subunit; KLRC1, killer cell lectin like receptor C1; LDLR, Low density lipoprotein receptor; MDSC, myeloid-derived suppressor cell; NK, natural killer; NKT, natural killer; NKG2A, natural killer cell lectin-like receptor subfamily C member 1; NECTIN2, Nectin Cell Adhesion Molecule 2; RNASE-2,Ribonuclease A Family Member 2; TRM, memory T cell; Treg, regulatory T cell; Teff, effector T cell; TIGIT, T cell immunoreceptor with Ig and ITIM domains; PD-1, Programmed Death-1; PDL-1, Programmed Cell Death-Ligand 1.

Figure 3

Related cells and molecules affecting hepatic ischemia-reperfusion injury. CXCL, C-X-C motif chemokine ligand; CCR7,CC-chemokine receptor 7; CXCR4, C-X-C chemokine receptor type 4; CSF3, colony stimulating factor 3; DC, dendritic cell; IRI, ischemia-reperfusion injury; HMGB-1, High Mobility Group protein B1; LCN2, Lipocalin-2; MRC1, Mannose Receptor C-type 1; MDSC, myeloid-derived suppressor cell; PTPRC,Protein Tyrosine Phosphatase, Receptor Type, C; ROS, reactive oxygen species; TRM, memory T cell; Treg, regulatory T cell; TNIP3, TNFAIP3 interacting protein 3; TLR4, Toll-like receptor 4; TIM-3, T-cell immunoglobulin and mucin domain 3.