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Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells. / Eymael, Jennifer; van den Broek, Martijn; Miesen, Laura et al.

In: Journal of pathology, Vol. 259, No. 2, 02.2023, p. 149-162.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

Eymael, J, van den Broek, M, Miesen, L, Monge, VV, van den Berge, BT, Mooren, F, Velez, VL, Dijkstra, J, Hermsen, M, Bándi, PT, Vermeulen, M, de Wildt, S, Willemsen, B, Florquin, S, Wetzels, R, Steenbergen, E, Kramann, R, Moeller, M, Schreuder, MF, Wetzels, JFM, van der Vlag, J, Jansen, J & Smeets, B 2023, 'Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells', Journal of pathology, vol. 259, no. 2, pp. 149-162. https://doi.org/10.1002/path.6029

APA

Eymael, J., van den Broek, M., Miesen, L., Monge, V. V., van den Berge, B. T., Mooren, F., Velez, V. L., Dijkstra, J., Hermsen, M., Bándi, P. T., Vermeulen, M., de Wildt, S., Willemsen, B., Florquin, S., Wetzels, R., Steenbergen, E., Kramann, R., Moeller, M., Schreuder, M. F., ... Smeets, B. (2023). Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells. Journal of pathology, 259(2), 149-162. https://doi.org/10.1002/path.6029

Vancouver

Eymael J, van den Broek M, Miesen L, Monge VV, van den Berge BT, Mooren F et al. Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells. Journal of pathology. 2023 Feb;259(2):149-162. Epub 2022. doi: 10.1002/path.6029

Author

Eymael, Jennifer ; van den Broek, Martijn ; Miesen, Laura et al. / Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells. In: Journal of pathology. 2023 ; Vol. 259, No. 2. pp. 149-162.

BibTeX

@article{a44ce6f59eec4633bedbb048d2222691,
title = "Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells",
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.",
keywords = "(mal-)adaptive repair, acute kidney injury, kidney regeneration, proximal tubule, scattered tubular cells",
author = "Jennifer Eymael and {van den Broek}, Martijn and Laura Miesen and Monge, {Valerie Villacorta} and {van den Berge}, {Bartholomeus T.} and Fieke Mooren and Velez, {Vicky Luna} and Jelmer Dijkstra and Meyke Hermsen and B{\'a}ndi, {P. ter} and Michiel Vermeulen and {de Wildt}, Saskia and Brigith Willemsen and Sandrine Florquin and Roy Wetzels and Eric Steenbergen and Rafael Kramann and Marcus Moeller and Schreuder, {Michiel F.} and Wetzels, {Jack F. M.} and {van der Vlag}, Johan and Jitske Jansen and Bart Smeets",
note = "Funding Information: JE is supported by the Dutch Kidney Foundation (Grant 14A3D104). MB is supported by the Dutch Kidney Foundation (Grant 19OK005). JJ is supported by the Netherlands Organization for Scientific Research (NWO Veni Grant 091 501 61 81 01 36) and the Dutch Kidney Foundation (Grant 19OK005). BS is supported by the Dutch Kidney Foundation (Grant 14A3D104) and the Netherlands Organization for Scientific Research (NWO VIDI Grant 016.156.363). Publisher Copyright: {\textcopyright} 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.",
year = "2023",
month = feb,
doi = "10.1002/path.6029",
language = "English",
volume = "259",
pages = "149--162",
journal = "Journal of pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

RIS

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, P. ter

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 - Funding Information: JE is supported by the Dutch Kidney Foundation (Grant 14A3D104). MB is supported by the Dutch Kidney Foundation (Grant 19OK005). JJ is supported by the Netherlands Organization for Scientific Research (NWO Veni Grant 091 501 61 81 01 36) and the Dutch Kidney Foundation (Grant 19OK005). BS is supported by the Dutch Kidney Foundation (Grant 14A3D104) and the Netherlands Organization for Scientific Research (NWO VIDI Grant 016.156.363). 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.

KW - (mal-)adaptive repair

KW - acute kidney injury

KW - kidney regeneration

KW - proximal tubule

KW - scattered tubular cells

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

VL - 259

SP - 149

EP - 162

JO - Journal of pathology

JF - Journal of pathology

SN - 0022-3417

IS - 2

ER -

ID: 29714745