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

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 high-quality cells to map healthy kidney at high resolution. Our sex-balanced dataset revealed sex-based differences in gene expression within proximal tubular cells, specifically, increased anti-oxidant metallothionein genes in females and the predominance of aerobic metabolism-related genes in males. Using CD45+ enrichment in 10 samples, we profile the immune niche of the kidney, identifying kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions. We observed significant heterogeneity in resident myeloid populations and identified an MRC1+ LYVE1+ FOLR2+ C1QC+ population as the predominant myeloid population in healthy kidney. This study provides a broad cellular map of healthy human kidney, revealing novel insights into the complexity of renal parenchymal cells and kidney-resident immune populations. Single -cell RNA sequencing (10X Genomics Single Cell 3’ v3) was performed on 19 core biopsies from human living donor kidneys, 9 biopsies from males and 10 from females. 10 samples (5 males, 5 females) were subjected to CD45-enrichment using magnetic EasySep Human CD45 depletion kit II (STEMCELL, cat# 17898).