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The renal papilla is a niche for adult kidney stem cells
Juan A. Oliver, … , Timothy P. Martens, Qais Al-Awqati
Juan A. Oliver, … , Timothy P. Martens, Qais Al-Awqati
Published September 15, 2004
Citation Information: J Clin Invest. 2004;114(6):795-804. https://doi.org/10.1172/JCI20921.
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Article Nephrology

The renal papilla is a niche for adult kidney stem cells

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Abstract

Many adult organs contain stem cells, which are pluripotent and are involved in organ maintenance and repair after injury. In situ, these cells often have a low cycling rate and locate in specialized regions (niches). To detect such cells in the kidney, we administered a pulse of the nucleotide bromodeoxyuridine (BrdU) to rat and mouse pups and, after a long (more than 2-month) chase, examined whether the kidney contained a population of low-cycling cells. We found that in the adult kidney, BrdU-retaining cells were very sparse except in the renal papilla, where they were numerous. During the repair phase of transient renal ischemia, these cells entered the cell cycle and the BrdU signal quickly disappeared from the papilla, despite the absence of apoptosis in this part of the kidney. In vitro isolation of renal papillary cells showed them to have a plastic phenotype that could be modulated by oxygen tension and that when injected into the renal cortex, they incorporated into the renal parenchyma. In addition, like other stem cells, papillary cells spontaneously formed spheres. Single-cell clones of these cells coexpressed mesenchymal and epithelial proteins and gave rise to myofibroblasts, cells expressing neuronal markers, and cells of uncharacterized phenotype. These data indicate that the renal papilla is a niche for adult kidney stem cells.

Authors

Juan A. Oliver, Omar Maarouf, Faisal H. Cheema, Timothy P. Martens, Qais Al-Awqati

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Figure 2

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BrdU-retaining cells in the adult kidney. (A_F) Composite views obtained...
BrdU-retaining cells in the adult kidney. (A_F) Composite views obtained by confocal microscopy with 1-μm optical sections, except where indicated otherwise (E and F). (A) Composite view 20 μm in thickness of a kidney cortex from a 3-month-old rat showing no BrdU-positive cells. g, glomerulus. (B) Composite view 10 μm in thickness of a glomerulus from a 2-month-old rat with a single BrdU-retaining cell in the glomerular tuft. (C) Composite view 20 μm in thickness of a kidney medulla from a 2-month-old rat with a single BrdU-retaining cell. (D) Composite view 20 μm in thickness of a kidney papilla from a 2-month-old rat showing numerous BrdU-positive cells. Arrows, interstitial cells; arrowheads, tubular cells. (E) Section 100 μm in thickness of a kidney papilla from a 3-month-old rat showing more fluorescent signal (i.e., BrdU) in the outer parts of the papilla. (F) Section 5 μm in thickness of the kidney papilla from a 5-month-old rat. (G) Composite view 20 μm in thickness of kidney papillary tubules from a 4-month-old rat showing that some of the BrdU-retaining cells are tubular epithelial cells expressing ZO-1 in their tight junctions. (H) Composite view 10 μm in thickness of a kidney medulla from a 3-month-old rat showing a single interstitial BrdU-retaining cell surrounded by collagen IV. (I) Composite view 20 μm in thickness of a kidney papilla from a 4-month-old rat showing BrdU-retaining cells in close association with endothelial cells. Scale bars: 50 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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