Single-cell omics in tracing cellular heterogeneity of drug-induced liver injury: Technological landscape and prospective application

Abstract

Drug-induced liver injury (DILI) remains a serious problem in clinics for both diagnoses and treatment decisions. It is a result of accumulated drugs in human bodies metabolized into toxic constituents generating reactive metabolites, and then arise initial consequences of oxidative stress, organelle stress responses, and lethal consequences (liver necrosis or apoptosis). However, the idiosyncratic nature of DILI complexes its mechanistic studies and still little is known of its potential etiopathogenesis for certain. Single-cell omics technology and approaches serve as powerful tools for investigating cellular heterogeneity and relationships from measurements of up to millions of individual cells at an unprecedented resolution, which are achieved by advances in genome, epigenome, transcriptome, proteome, and metabolism technologies. As liver contains heterogeneous cell types of distinct spatial, molecular, and functional properties, they interact with each other to precede cell type-specific omics reprogramming and play an irreplaceable role in liver cells with heterogeneous properties upon encountering toxic insults. Single-cell omics, especially single-cell transcriptomics and single-cell proteomics, have been utilized for exploring the mechanisms of DILI and prediction for risk factors. In this review, we discuss the recent development and future perspectives of single-cell omics-based technologies for DILI-related research.