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; Sarah Q Crome

doi:10.1038/s41467-022-35297-z

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

Nat Commun. 2022 Dec 10;13(1):7634. doi: 10.1038/s41467-022-35297-z.

Authors

Caitriona M McEvoy^#^{1

2

3}, Julia M Murphy^#^{1

2

4}, Lin Zhang^{5

6}, Sergi Clotet-Freixas^{1

2}, Jessica A Mathews^{1

2}, James An^{1

2

4}, Mehran Karimzadeh^{6

7}, Delaram Pouyabahar^{8

9}, Shenghui Su^{1

2}, Olga Zaslaver^{8

9}, Hannes Röst^{8

9}, Rangi Arambewela^{1

2}, Lewis Y Liu^{1

2

4}, Sally Zhang¹⁰, Keith A Lawson¹⁰, Antonio Finelli^{10

11}, Bo Wang^{6

7

12

13}, Sonya A MacParland^{1

2

4

13}, Gary D Bader^{8

9

12

14

15}, Ana Konvalinka^{16

17

18

19

20}, Sarah Q Crome^{21

22

23}

Affiliations

¹ Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
² Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada.
³ Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON, Canada.
⁴ Department of Immunology, University of Toronto, Toronto, ON, Canada.
⁵ Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada.
⁶ Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
⁷ Vector Institute, Toronto, ON, Canada.
⁸ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁹ The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
¹⁰ Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
¹¹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
¹² Department of Computer Science, University of Toronto, Toronto, ON, Canada.
¹³ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
¹⁴ Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
¹⁵ The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
¹⁶ Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada. Ana.Konvalinka@uhn.ca.
¹⁷ Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada. Ana.Konvalinka@uhn.ca.
¹⁸ Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON, Canada. Ana.Konvalinka@uhn.ca.
¹⁹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Ana.Konvalinka@uhn.ca.
²⁰ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Ana.Konvalinka@uhn.ca.
²¹ Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada. sarah.crome@utoronto.ca.
²² Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada. sarah.crome@utoronto.ca.
²³ Department of Immunology, University of Toronto, Toronto, ON, Canada. sarah.crome@utoronto.ca.

^# Contributed equally.

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.

MeSH terms

Female
Folate Receptor 2* / metabolism
Gene Expression Profiling
Humans
Kidney* / metabolism
Male
Metallothionein / genetics
Metallothionein / metabolism
Myeloid Cells / metabolism
Single-Cell Analysis
Transcriptome

Substances

Metallothionein
FOLR2 protein, human
Folate Receptor 2

Abstract

MeSH terms

Substances

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