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

被引：30
作者：
McEvoy, Caitriona M. [1 ,2 ,3 ]
Murphy, Julia M. [1 ,2 ,4 ]
Zhang, Lin [5 ,6 ]
Clotet-Freixas, Sergi [1 ,2 ]
Mathews, Jessica A. [1 ,2 ]
An, James [1 ,2 ,4 ]
Karimzadeh, Mehran [6 ,7 ]
Pouyabahar, Delaram [8 ,9 ]
Su, Shenghui [1 ,2 ]
Zaslaver, Olga [8 ,9 ]
Roest, Hannes [8 ,9 ]
Arambewela, Rangi [1 ,2 ]
Liu, Lewis Y. [1 ,2 ,4 ]
Zhang, Sally [10 ]
Lawson, Keith A. [10 ]
Finelli, Antonio [10 ,11 ]
Wang, Bo [6 ,7 ,12 ,13 ]
MacParland, Sonya A. [1 ,2 ,4 ,13 ]
Bader, Gary D. [8 ,9 ,12 ,14 ,15 ]
Konvalinka, Ana [1 ,2 ,3 ,11 ,13 ]
Crome, Sarah Q. [1 ,2 ,4 ]
机构：
[1] Univ Hlth Network, Toronto Gen Hosp Res Inst, Toronto, ON, Canada
[2] Univ Hlth Network, Ajmera Transplant Ctr, Toronto, ON, Canada
[3] Univ Hlth Network, Div Nephrol, Dept Med, Toronto, ON, Canada
[4] Univ Toronto, Dept Immunol, Toronto, ON, Canada
[5] Univ Toronto, Dept Stat Sci, Toronto, ON, Canada
[6] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada
[7] Vector Inst, Toronto, ON, Canada
[8] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
[9] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada
[10] Univ Hlth Network, Princess Margaret Canc Ctr, Div Urol, Toronto, ON, Canada
[11] Univ Toronto, Inst Med Sci, Toronto, ON, Canada
[12] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada
[13] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[14] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada
[15] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada
来源：
NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期
基金：
加拿大创新基金会; 美国国家卫生研究院;
关键词：
TUBULAR CELLS; AMINO-ACIDS; METALLOTHIONEIN; METABOLISM; EXPRESSION; INJURY; ACTIVATION; DISEASE; MACROPHAGES; INDICATOR;
D O I：
10.1038/s41467-022-35297-z
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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. Knowledge of the transcriptional programs of human kidney cell populations at homeostasis is limited. Here, the authors show sex-based differences in gene expression of kidney parenchymal cells and examine the complexity of kidney-resident immune cells using single cell RNA sequencing of healthy living kidney donors.
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页数：18
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