Revealing the Heterogeneity of Renal Tubular Epithelial Cell Senescence and Its Impact on Renal Fibrosis via Single‐Cell Sequencing and Spatial Omics Technologies

The global incidence of chronic kidney diseases (CKD) continues to rise annually, with renal fibrosis (RF) identified as the primary pathological mechanism leading to end-stage renal disease. The senescence of renal tubular epithelial cells (RTECs) has been established as a significant factor driving the progression of RF. Cellular senescence represents a fundamental cellular response to stress, characterized by irreversible cell cycle arrest and the emergence of senescent secretory phenotypes (SASP). Traditional studies have predominantly treated RTECs as homogeneous entities, complicating the understanding of their functional differences throughout the aging process and their specific regulatory roles within the microenvironment. Recent advancements in Single-cell Sequencing (sc-seq) and Spatial Omics technologies have equipped researchers with robust tools to analyze the heterogeneous characteristics of aging in RTECs, identify their spatial distribution patterns, and elucidate the causal relationships with fibrosis. This article systematically reviews the application of sc-seq and spatial omics techniques in uncovering the aging heterogeneity of RTECs, while thoroughly analyzing the molecular characteristics and spatial distribution patterns of aging subpopulations, as well as the mechanisms by which they influence RF. These findings will offer new insights for further investigations into RF and CKD, providing a theoretical foundation and technical support for the precise diagnosis and targeted treatment of CKD.