Differentiated kidney epithelial cells repair injured proximal tubule
- PMID: 24127583
- PMCID: PMC3910580
- DOI: 10.1073/pnas.1310653110
Differentiated kidney epithelial cells repair injured proximal tubule
Erratum in
- Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5754
Abstract
Whether kidney proximal tubule harbors a scattered population of epithelial stem cells is a major unsolved question. Lineage-tracing studies, histologic characterization, and ex vivo functional analysis results conflict. To address this controversy, we analyzed the lineage and clonal behavior of fully differentiated proximal tubule epithelial cells after injury. A CreER(T2) cassette was knocked into the sodium-dependent inorganic phosphate transporter SLC34a1 locus, which is expressed only in differentiated proximal tubule. Tamoxifen-dependent recombination was absolutely specific to proximal tubule. Clonal analysis after injury and repair showed that the bulk of labeled cells proliferate after injury with increased clone size after severe compared with mild injury. Injury to labeled proximal tubule epithelia induced expression of CD24, CD133, vimentin, and kidney-injury molecule-1, markers of putative epithelial stem cells in the human kidney. Similar results were observed in cultured proximal tubules, in which labeled clones proliferated and expressed dedifferentiation and injury markers. When mice with completely labeled kidneys were subject to injury and repair there was no dilution of fate marker despite substantial proliferation, indicating that unlabeled progenitors do not contribute to kidney repair. During nephrogenesis and early kidney growth, single proximal tubule clones expanded, suggesting that differentiated cells also contribute to tubule elongation. These findings provide no evidence for an intratubular stem-cell population, but rather indicate that terminally differentiated epithelia reexpress apparent stem-cell markers during injury-induced dedifferentiation and repair.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
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Comment in
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CD133 might be a pan marker of epithelial cells with dedifferentiation capacity.Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):E1451-2. doi: 10.1073/pnas.1400195111. Epub 2014 Mar 20. Proc Natl Acad Sci U S A. 2014. PMID: 24706908 Free PMC article. No abstract available.
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Reply to Corbeil et al.: Dedifferentiation and multipotency.Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):E1453. doi: 10.1073/pnas.1401733111. Proc Natl Acad Sci U S A. 2014. PMID: 24851265 Free PMC article. No abstract available.
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References
-
- Amdur RL, Chawla LS, Amodeo S, Kimmel PL, Palant CE. Outcomes following diagnosis of acute renal failure in U.S. veterans: Focus on acute tubular necrosis. Kidney Int. 2009;76(10):1089–1097. - PubMed
-
- Witzgall R, Brown D, Schwarz C, Bonventre JV. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest. 1994;93(5):2175–2188. - PMC - PubMed
-
- Humphreys BD, et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008;2(3):284–291. - PubMed
-
- Sagrinati C, et al. Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J Am Soc Nephrol. 2006;17(9):2443–2456. - PubMed
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