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

Amin Abedini, Yuan O. Zhu, Shatakshee Chatterjee, Gabor Halasz, Kishor Devalaraja-Narashimha, Rojesh Shrestha, Michael S. Balzer, Jihwan Park, Tong Zhou, Ziyuan Ma, Katie Marie Sullivan, Hailong Hu, Xin Sheng, Hongbo Liu, Yi Wei, Carine M. Boustany-Kari, Uptal Patel, Salem Almaani, Matthew Palmer, Raymond Townsend, Shira Blady, Jonathan Hogan, Lori Morton, Katalin Susztak and The TRIDENT Study Investigators*
JASN February 2021, ASN.2020050757; DOI: https://doi.org/10.1681/ASN.2020050757
Amin Abedini
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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  • ORCID record for Amin Abedini
Yuan O. Zhu
4Cardiovascular, Renal and Fibrosis Research, Regeneron Pharmaceuticals Inc., Tarrytown, New York
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Shatakshee Chatterjee
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Gabor Halasz
4Cardiovascular, Renal and Fibrosis Research, Regeneron Pharmaceuticals Inc., Tarrytown, New York
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Kishor Devalaraja-Narashimha
4Cardiovascular, Renal and Fibrosis Research, Regeneron Pharmaceuticals Inc., Tarrytown, New York
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Rojesh Shrestha
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Michael S. Balzer
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Jihwan Park
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Tong Zhou
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Ziyuan Ma
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Katie Marie Sullivan
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Hailong Hu
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Xin Sheng
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Hongbo Liu
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Yi Wei
4Cardiovascular, Renal and Fibrosis Research, Regeneron Pharmaceuticals Inc., Tarrytown, New York
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Carine M. Boustany-Kari
5Cardiometabolic Disease Research Department, Boehringer Ingelheim, Ridgefield, Connecticut
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Uptal Patel
6Inflammation and Respiratory Therapeutics, Gilead Sciences Inc., Foster City, California
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Salem Almaani
7Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio
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Matthew Palmer
8Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Raymond Townsend
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Shira Blady
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Jonathan Hogan
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Lori Morton
4Cardiovascular, Renal and Fibrosis Research, Regeneron Pharmaceuticals Inc., Tarrytown, New York
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Katalin Susztak
1Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
3Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Significance Statement

Microscopic analysis of urinary sediment is one of the most fundamental tests in nephrology. Urinary cells, however, have not been characterized in a standardized, unbiased manner. Single-cell transcriptomics of urine, of subjects with diabetic kidney disease and controls, were used to characterize 23,082 urinary cells in an unbiased manner. Combined analysis of urinary, kidney, and bladder cells indicated the technique can detect almost all kidney cell types and a variety of bladder cell types in human urine. This pilot study provides a reference dataset for future urinary single-cell characterization.

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.

  • diabetic kidney disease
  • urine
  • single-cell transcriptomics
  • RNA sequencing
  • Copyright © 2021 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 32 (2)
Journal of the American Society of Nephrology
Vol. 32, Issue 2
February 2021
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Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney
Amin Abedini, Yuan O. Zhu, Shatakshee Chatterjee, Gabor Halasz, Kishor Devalaraja-Narashimha, Rojesh Shrestha, Michael S. Balzer, Jihwan Park, Tong Zhou, Ziyuan Ma, Katie Marie Sullivan, Hailong Hu, Xin Sheng, Hongbo Liu, Yi Wei, Carine M. Boustany-Kari, Uptal Patel, Salem Almaani, Matthew Palmer, Raymond Townsend, Shira Blady, Jonathan Hogan, Lori Morton, Katalin Susztak, The TRIDENT Study Investigators*
JASN Feb 2021, ASN.2020050757; DOI: 10.1681/ASN.2020050757

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Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney
Amin Abedini, Yuan O. Zhu, Shatakshee Chatterjee, Gabor Halasz, Kishor Devalaraja-Narashimha, Rojesh Shrestha, Michael S. Balzer, Jihwan Park, Tong Zhou, Ziyuan Ma, Katie Marie Sullivan, Hailong Hu, Xin Sheng, Hongbo Liu, Yi Wei, Carine M. Boustany-Kari, Uptal Patel, Salem Almaani, Matthew Palmer, Raymond Townsend, Shira Blady, Jonathan Hogan, Lori Morton, Katalin Susztak, The TRIDENT Study Investigators*
JASN Feb 2021, ASN.2020050757; DOI: 10.1681/ASN.2020050757
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