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 Fm Wetzels; Johan van der Vlag; Jitske Jansen; Bart Smeets

doi:10.1002/path.6029

Publisher Website

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

Authors

Eymael, Jennifer¹
van den Broek, Martijn^{1, 2}
Miesen, Laura¹
Monge, Valerie Villacorta¹
van den Berge, Bartholomeus T^{1, 3}
Mooren, Fieke¹
Velez, Vicky Luna⁴
Dijkstra, Jelmer⁴
Hermsen, Meyke¹
Bándi, Péter¹
Vermeulen, Michiel⁴
de Wildt, Saskia⁵
Willemsen, Brigith¹
Florquin, Sandrine^{6, 7}
Wetzels, Roy¹
Steenbergen, Eric¹
Kramann, Rafael^{8, 9, 10}
Moeller, Marcus⁸
Schreuder, Michiel F²
Wetzels, Jack Fm^{3, 11}
van der Vlag, Johan³
Jansen, Jitske^{1, 2, 9}
Smeets, Bart¹

And 3 more

¹ Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. , (Netherlands)
² Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands. , (Mali)
³ Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. , (Netherlands)
⁴ Department of Molecular Biology, Radboud Institute for Molecular Life Science, Nijmegen, The Netherlands. , (Netherlands)
⁵ Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Science, Nijmegen, The Netherlands. , (Netherlands)
⁶ Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. , (Netherlands)
⁷ Amsterdam Institute for Infection and Immunology, Amsterdam, The Netherlands. , (Netherlands)
⁸ Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany. , (Germany)
⁹ Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany. , (Germany)
¹⁰ Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands. , (Netherlands)
¹¹ Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. , (Netherlands)

Type

Published Article

Journal

The Journal of Pathology

Publisher

Wiley (John Wiley & Sons)

Publication Date

Feb 01, 2023

Volume

259

Issue

2

Pages

149–162

Identifiers

DOI: 10.1002/path.6029

PMID: 36373978

Source

Medline

Keywords

Language

English

License

Unknown

Abstract

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. This record was last updated on 04/28/2023 and may not reflect the most current and accurate biomedical/scientific data available from NLM. The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/36373978

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