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

Author

Listed:
  • Caitriona M. McEvoy

    (University Health Network
    University Health Network
    University Health Network)

  • Julia M. Murphy

    (University Health Network
    University Health Network
    University of Toronto)

  • Lin Zhang

    (University of Toronto
    University Health Network)

  • Sergi Clotet-Freixas

    (University Health Network
    University Health Network)

  • Jessica A. Mathews

    (University Health Network
    University Health Network)

  • James An

    (University Health Network
    University Health Network
    University of Toronto)

  • Mehran Karimzadeh

    (University Health Network
    Vector Institute)

  • Delaram Pouyabahar

    (University of Toronto
    University of Toronto)

  • Shenghui Su

    (University Health Network
    University Health Network)

  • Olga Zaslaver

    (University of Toronto
    University of Toronto)

  • Hannes Röst

    (University of Toronto
    University of Toronto)

  • Rangi Arambewela

    (University Health Network
    University Health Network)

  • Lewis Y. Liu

    (University Health Network
    University Health Network
    University of Toronto)

  • Sally Zhang

    (University Health Network)

  • Keith A. Lawson

    (University Health Network)

  • Antonio Finelli

    (University Health Network
    University of Toronto)

  • Bo Wang

    (University Health Network
    Vector Institute
    University of Toronto
    University of Toronto)

  • Sonya A. MacParland

    (University Health Network
    University Health Network
    University of Toronto
    University of Toronto)

  • Gary D. Bader

    (University of Toronto
    University of Toronto
    University of Toronto
    University Health Network)

  • Ana Konvalinka

    (University Health Network
    University Health Network
    University Health Network
    University of Toronto)

  • Sarah Q. Crome

    (University Health Network
    University Health Network
    University of Toronto)

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.

Suggested Citation

  • 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 Ar, 2022. "Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35297-z
    DOI: 10.1038/s41467-022-35297-z
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