Spatial transcriptomics in glomerular diseases

Abstract Spatial transcriptomics enables the study of the mechanisms of disease through gene expression and pathway activity analysis in a spatial context. Originally mainly employed in oncology, the techniques developed use different methods of transcript identification, resolution (single cells vs regions), flexibility of target regions and the type of molecules that can be assessed (RNA and/or protein). Selection of regions of interest requires both knowledge of the underlying histopathological changes and limitations of the methods, like artefacts due to variation in pre-analytics, or the probes used to analyse them. Here we review techniques currently available, their opportunities and limitations and discuss results obtained using Digital Spatial Profiling in pauci-immune focal necrotizing (and crescentic) glomerulonephritis (piFNGN) and giant cells arteritis (GCA). Spatial profiling techniques are powerful tools to investigate defined regions of interest in autoimmune and inflammatory disorders and allow for the identification of genes differentially expressed between different types of lesions and different disease aetiologies. Spatial profiling provides an example of a powerful methodology to investigate disease pathways in tissue at a local level across a spectrum of human diseases and generates hypotheses about molecular mechanisms that can be further investigated in detail. When implemented in the setting of a systems biology approach it may ultimately reach the goal of predicting the course of disease from histopathological slides.