TY - JOUR
T1 - Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells
AU - Eymael, Jennifer
AU - van den Broek, Martijn
AU - Miesen, Laura
AU - Monge, Valerie Villacorta
AU - van den Berge, Bartholomeus T.
AU - Mooren, Fieke
AU - Velez, Vicky Luna
AU - Dijkstra, Jelmer
AU - Hermsen, Meyke
AU - Bándi, Péter
AU - Vermeulen, Michiel
AU - de Wildt, Saskia
AU - Willemsen, Brigith
AU - Florquin, Sandrine
AU - Wetzels, Roy
AU - Steenbergen, Eric
AU - Kramann, Rafael
AU - Moeller, Marcus
AU - Schreuder, Michiel F.
AU - Wetzels, Jack F.M.
AU - van der Vlag, Johan
AU - Jansen, Jitske
AU - Smeets, Bart
N1 - Publisher Copyright:
© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
PY - 2023/2
Y1 - 2023/2
N2 - 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+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 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.
AB - 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+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 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.
UR - http://www.scopus.com/inward/record.url?scp=85144248949&partnerID=8YFLogxK
U2 - 10.1002/path.6029
DO - 10.1002/path.6029
M3 - Article
C2 - 36373978
AN - SCOPUS:85144248949
SN - 0022-3417
VL - 259
SP - 149
EP - 162
JO - Journal of Pathology
JF - Journal of Pathology
IS - 2
ER -