PRJNA799138
Single-cell sequencing reveals homogeneity and heterogeneity in the molecular cytopathological mechanisms of AKI caused by different etiologies
Acute kidney injury (AKI) is a complex acute stress injury event which can be induced by multiple triggers. The potential homo- and heterogeneity of injury patterns in different etiology-induced AKI are poorly understood. Here, we performed single-cell transcriptome sequencing of mouse kidneys from five common AKI models (cisplatin, folic acid, sodium oxalate, ischemia-reperfusion injury, and unilateral ureteral obstruction). Our data show that extensive cell death and cytoskeletal remodeling events in proximal tubular cells (PTCs), as well as aberrant proliferation and inflammation in endothelial cells (ECs) are common injury patterns among different AKI models. While PTCs show different susceptibility to death pattern and injury outcome, Pro- and injured-ECs also possess different transcriptional characteristics in different AKI models. Although the proportion of immune cell infiltration varied considerably in different AKI models, the intercellular signaling patterns were highly similar, with active M1 and M2 macrophage surface CD74 acting as a ligand/receptor to extensively activate the immunostimulatory effects of parenchymal cells. Furthermore, using proteomics, phosphorylated proteomics, public databases, and immunohistochemistry, we confirm that the cytoskeleton remodeling-related proteins Tmsb4x and Arpc1b are likely novel biomarkers of AKI. Taken together, we have mapped the most comprehensive multi-model AKI single-cell atlas to date. Further, our study explores the homogeneity of injury and model heterogeneity in AKI due to different etiologies, thus providing a benchmark for future insightful studies.