Improved understanding of the cellular changes and interactions that occur in the kidney following injury may help to elucidate the mechanisms that govern the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) and aid the development of therapeutic interventions. In new research, Michal Polonsky, Louisa Gerhardt and colleagues use single-cell spatial transcriptomics to uncover injury-specific and spatially dependent gene expression patterns in distinct cellular microenvironments within the mouse kidney following ischaemia–reperfusion injury.

Using sequential fluorescence in situ hybridization (seqFISH), the researchers identified 17 microenvironments, comprising neighbourhoods of distinct cell type compositions within the kidney. Nine of the microenvironments differed between healthy control and injured samples. One of these, ME-5, contained the highest density of injured proximal tubule cells, as well as fibroblasts and immune cells, in the AKI samples. Analyses of ligand–receptor interactions within ME-5 identified an upregulation of CLCF1–CRLF1 signalling between persistently injured proximal tubule cells and their neighbouring fibroblasts. Another microenvironment, ME-16, resembled a tertiary lymphoid structure, containing CD4+ T cells and T regulatory cells, as well as pro-inflammatory macrophages.