Single-cell and transcriptome analysis reveals TAL cells in diabetic nephropathy

Abstract

Diabetic nephropathy is a global public health concern with multifaceted pathogenesis, primarily involving hypertension. Excessive activation of AT1R has been strongly associated with hypertension onset and progression in diabetic nephropathy. This study aimed to conduct thick ascending limb cell single-cell and transcriptomic analysis in diabetic nephropathy, including screening for biological markers, cellular communication, and immune infiltration, to identify potential biomarkers and effective means for prevention and treatment. By using high-dimensional weighted gene co-expression network analysis, Least Absolute Shrinkage and Selection Operator, machine learning, neural deconvolution, quasi-chronological analysis, Non-negative Matrix Factorization clustering, and Monocyte Chemotactic Protein-induced Counter, we identified 7 potential thick ascending limb cell biomarkers for diabetic nephropathy and elucidated the Bone Morphogenetic Protein pathway's regulation of thick ascending limb cells through podocyte epithelial cells and podocyte cells. The study also highlighted the role of COBL, PPARGC1A, and THSD7A in Non-negative Matrix Factorization clustering and their relationship with thick ascending limb cell immunity in diabetic nephropathy. Our findings provide new insights and avenues for managing diabetic nephropathy, ultimately alleviating the burden on patients and society.