Dataset Information

Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney.

ABSTRACT:

Background

Microscopic analysis of urine sediment is probably the most commonly used diagnostic procedure in nephrology. The urinary cells, however, have not yet undergone careful unbiased characterization.

Methods

Single-cell transcriptomic analysis was performed on 17 urine samples obtained from five subjects at two different occasions, using both spot and 24-hour urine collection. A pooled urine sample from multiple healthy individuals served as a reference control. In total 23,082 cells were analyzed. Urinary cells were compared with human kidney and human bladder datasets to understand similarities and differences among the observed cell types.

Results

Almost all kidney cell types can be identified in urine, such as podocyte, proximal tubule, loop of Henle, and collecting duct, in addition to macrophages, lymphocytes, and bladder cells. The urinary cell-type composition was subject specific and reasonably stable using different collection methods and over time. Urinary cells clustered with kidney and bladder cells, such as urinary podocytes with kidney podocytes, and principal cells of the kidney and urine, indicating their similarities in gene expression.

Conclusions

A reference dataset for cells in human urine was generated. Single-cell transcriptomics enables detection and quantification of almost all types of cells in the kidney and urinary tract.

SUBMITTER: Abedini A

PROVIDER: S-EPMC7920183 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney.

Abedini Amin A Zhu Yuan O YO Chatterjee Shatakshee S Halasz Gabor G Devalaraja-Narashimha Kishor K Shrestha Rojesh R S Balzer Michael M Park Jihwan J Park Jihwan J Zhou Tong T Ma Ziyuan Z Sullivan Katie Marie KM Hu Hailong H Sheng Xin X Liu Hongbo H Wei Yi Y Boustany-Kari Carine M CM Patel Uptal U Almaani Salem S Palmer Matthew M Townsend Raymond R Blady Shira S Hogan Jonathan J Morton Lori L Susztak Katalin K

Journal of the American Society of Nephrology : JASN 20210202 3

<h4>Background</h4>Microscopic analysis of urine sediment is probably the most commonly used diagnostic procedure in nephrology. The urinary cells, however, have not yet undergone careful unbiased characterization.<h4>Methods</h4>Single-cell transcriptomic analysis was performed on 17 urine samples obtained from five subjects at two different occasions, using both spot and 24-hour urine collection. A pooled urine sample from multiple healthy individuals served as a reference control. In total 23 ...[more]

PMID: 33531352

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Project description:BackgroundThe standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable.MethodsWe prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression.ResultsA three-gene signature of 18S ribosomal (rRNA)-normalized measures of CD3ε mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operating-characteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer-Lemeshow test indicated good fit (P=0.77). In an external-validation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P=0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti-interleukin-2 receptor antibodies from those who received T-cell-depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P=0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001).ConclusionsA molecular signature of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts. (Funded by the National Institutes of Health and others.).

Dataset Information

Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney.

Background

Methods

Results

Conclusions

Publications

Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney.

Similar Datasets

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