Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells.

Scattered tubular cells (STCs) are a phenotypically distinct cell population in the proximal tubule that increase in number after acute kidney injury. We aimed to characterize the human STC population. Three-dimensional human tissue analysis revealed that STCs are preferentially located within inner bends of the tubule, are barely present in young kidney tissue (<2 years) and their number increases with age. Increased STC numbers were associated with acute tubular injury (kidney injury molecule 1) and interstitial fibrosis (alpha smooth muscle actin). Isolated CD13 + CD24 - CD133 - proximal tubule epithelial cells (PTECs) and CD13 + CD24+ and CD13 + CD133 + STCs were analyzed using RNA sequencing. Transcriptome analysis revealed an upregulation of nuclear factor kappa-B, tumor necrosis factor alpha and inflammatory pathways in STCs, whereas metabolism, especially the tricarboxylic acid cycle and oxidative phosphorylation were downregulated, without showing signs of cellular senescence. Using immunostaining and a publicly available single-cell sequencing database of human kidneys, we indicated that STCs represent a heterogeneous population in a transient state. In conclusion, STCs are dedifferentiated PTECs showing a metabolic shift towards glycolysis, which could facilitate cellular survival after kidney injury. This article is protected by copyright. All rights reserved.