Resource and Technical AdvanceIn-Press PreviewNephrology
Open Access | 10.1172/jci.insight.146374
1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
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6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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Lin, F.
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
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7Department of Pathology, Columbia University Medical Center, New York, United States of America
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1Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, United States of America
2Department of Biomedical Informatics, Columbia University Medical Center, New York, United States of America
3Department of Medicine, Division of Nephrology, University of Washington, Seattle, United States of America
4Department of Biomedical Engineering, Columbia University Medical Center, New York, United States of America
5Department of Pediatrics, Columbia University Medical Center, New York, United States of America
6Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States of America
7Department of Pathology, Columbia University Medical Center, New York, United States of America
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Published March 1, 2022 - More info
The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not specifically assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours. To detect acute responses to clinically relevant stimuli, we created Rosa26-floxed-stop uracil phosphoribosyl-transferase (Uprt) expressing mice and inoculated 4-thiouracil (TU) to tag nascent RNA at selected time points. Cre-driven TU-tagged RNA was isolated from whole kidneys and demonstrated that volume depletion and ischemia induced different genetic programs. Even lineage related cell types expressed different genes in response to the two stressors. TU-tagging also demonstrated the transient nature of the responses. Because we placed Uprt in the ubiquitously active Rosa-26 locus, RNAs from many cell types can be tagged in vivo and their roles interrogated under various conditions. In short, TU labeling identifies stimulus-specific, cell-specific, and time-dependent acute responses that are otherwise difficult to detect with other technologies and are entirely obscured when sCr is the sole metric of kidney damage.