Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity

Caitriona M. McEvoy, Julia M. Murphy, Lin Zhang, Sergi Clotet-Freixas, Jessica A. Mathews, James An, Mehran Karimzadeh, Delaram Pouyabahar, Shenghui Su, Olga Zaslaver, Hannes Röst, Rangi Arambewela, Lewis Y. Liu, Sally Zhang, Keith A. Lawson, Antonio Finelli, Bo Wang, Sonya A. MacParland, Gary D. Bader, Ana Konvalinka () and Sarah Q. Crome ()
Additional contact information
Caitriona M. McEvoy: University Health Network
Julia M. Murphy: University Health Network
Lin Zhang: University of Toronto
Sergi Clotet-Freixas: University Health Network
Jessica A. Mathews: University Health Network
James An: University Health Network
Mehran Karimzadeh: University Health Network
Delaram Pouyabahar: University of Toronto
Shenghui Su: University Health Network
Olga Zaslaver: University of Toronto
Hannes Röst: University of Toronto
Rangi Arambewela: University Health Network
Lewis Y. Liu: University Health Network
Sally Zhang: University Health Network
Keith A. Lawson: University Health Network
Antonio Finelli: University Health Network
Bo Wang: University Health Network
Sonya A. MacParland: University Health Network
Gary D. Bader: University of Toronto
Ana Konvalinka: University Health Network
Sarah Q. Crome: University Health Network

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Knowledge of the transcriptional programs underpinning the functions of human kidney cell populations at homeostasis is limited. We present a single-cell perspective of healthy human kidney from 19 living donors, with equal contribution from males and females, profiling the transcriptome of 27677 cells to map human kidney at high resolution. Sex-based differences in gene expression within proximal tubular cells were observed, specifically, increased anti-oxidant metallothionein genes in females and aerobic metabolism-related genes in males. Functional differences in metabolism were confirmed in proximal tubular cells, with male cells exhibiting higher oxidative phosphorylation and higher levels of energy precursor metabolites. We identified kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions. Significant heterogeneity in myeloid cells was observed, with a MRC1+LYVE1+FOLR2+C1QC+ population representing a predominant population in healthy kidney. This study provides a detailed cellular map of healthy human kidney, and explores the complexity of parenchymal and kidney-resident immune cells.

Date: 2022
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DOI: 10.1038/s41467-022-35297-z

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