Applying single-cell technologies to clinical pathology: progress in nephropathology

Cells represent the basic building blocks of living organisms. Accurate characterisation of cellular phenotype, intercellular signalling networks, and the spatial organisation of cells within organs is crucial to deliver a better understanding of the processes underpinning physiology, and the perturbations that lead to disease. Single-cell methodologies have increased rapidly in scale and scope in recent years and are set to generate important insights into human disease. Here, we review current practices in nephropathology, which are dominated by relatively simple morphological descriptions of tissue biopsies based on their appearance using light microscopy. Bulk transcriptomics have more recently been used to explore glomerular and tubulointerstitial kidney disease, renal cancer, and the responses to injury and alloimmunity in kidney transplantation, generating novel disease insights and prognostic biomarkers. These studies set the stage for single-cell transcriptomic approaches that reveal cell-type-specific gene expression patterns in health and disease. These technologies allow genome-wide disease susceptibility genes to be interpreted with the knowledge of the specific cell populations within organs that express them, identifying candidate cell types for further study. Single-cell technologies are also moving beyond assaying individual cellular transcriptomes, to measuring the epigenetic landscape of single cells. Single-cell antigen-receptor gene sequencing also enables specific T- and B-cell clones to be tracked in different tissues and disease states. In the coming years these rich 'multi-omic' descriptions of kidney disease will enable histopathological descriptions to be comprehensively integrated with molecular phenotypes, enabling better disease classification and prognostication and the application of personalised treatment strategies. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.