Single-Cell and Spatial Transcriptomics in Renal Injury and Fibrosis Research

Kidney diseases, which are broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD), represent a significant and ongoing health burden in China and across the globe. AKI is a clinical syndrome marked by a rapid decline in renal function within 48 h due to diverse causes. Despite its high prevalence among hospitalized patients as a common complication, current therapeutic outcomes remain unsatisfactory. Therefore, a critical step toward resolving this issue is the precise identification of the specific cell types that drive renal regeneration during AKI repair. Renal fibrosis, pathologically characterized by excessive extracellular matrix (ECM) deposition, is the common final pathway of CKD and significantly impairs patient's quality of life and prognosis. The focal nature of fibrotic lesions has prompted systematic investigations into the fibrotic microenvironment. Myofibroblasts are the central effector cells driving pathological ECM deposition. Nevertheless, their cellular origins remain elusive. A thorough understanding of myofibroblast origins, along with the composition and regulatory factors of the fibrotic microenvironment, is therefore crucial for developing effective treatments for renal fibrosis.

The kidney is a complex organ with intricate anatomical structures and diverse cellular composition. Traditional investigative methods which rely on conventional pathology and low-resolution molecular biology have been unable to capture cellular heterogeneity at single-cell resolution. This limitation has obscured functional distinctions among cell subpopulations and their critical spatial context, thereby leading to an inadequate understanding of intercellular communication. Fortunately, the advent of single-cell and spatial transcriptomics has revolutionized kidney research by enabling comprehensive profiling of functional signatures and intercellular crosstalk within the renal microenvironment.

This review summarizes the current applications of single-cell and spatial transcriptomics in renal regeneration and fibrosis. Furthermore, it introduces emerging technologies, such as proximity-dependent labeling, while rarely applied in kidney research to date, hold significant potential. Our aim is to provide researchers with insightful strategies for their future application in this field.