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

Jennifer Eymael, Martijn van den Broek, Laura Miesen, Valerie Villacorta Monge, Bartholomeus T. van den Berge, Fieke Mooren, Vicky Luna Velez, Jelmer Dijkstra, Meyke Hermsen, Péter Bándi, Michiel Vermeulen, Saskia de Wildt, Brigith Willemsen, Sandrine Florquin, Roy Wetzels, Eric Steenbergen, Rafael Kramann, Marcus Moeller, Michiel F. Schreuder, Jack F.M. WetzelsJohan van der Vlag, Jitske Jansen, Bart Smeets*

*Corresponding author for this work

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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 and 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+CD24CD133 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 κB, tumor necrosis factor alpha, and inflammatory pathways in STCs, whereas metabolism, especially the tricarboxylic acid cycle and oxidative phosphorylation, was downregulated, without showing signs of cellular senescence. Using immunostaining and a publicly available single-cell sequencing database of human kidneys, we demonstrate that STCs represent a heterogeneous population in a transient state. In conclusion, STCs are dedifferentiated PTECs showing a metabolic shift toward glycolysis, which could facilitate cellular survival after kidney injury.

Original languageEnglish
Pages (from-to)149-162
Number of pages14
JournalJournal of Pathology
Issue number2
Early online date14 Nov 2022
Publication statusPublished - Feb 2023

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© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


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