Single-cell profiling reveals sex diversity in human renal proximal tubules

Gene. 2020 Aug 20:752:144790. doi: 10.1016/j.gene.2020.144790. Epub 2020 May 18.

Abstract

Many anatomical regions in the kidney, including proximal tubules, differ between males and females. While such differences in renal structures and functions under various physiological and pharmacological conditions have been identified, information relating to molecular mechanisms behind this gender disparity remain unknown. To understand gene expression differences in proximal tubules from human male and female kidneys, we reported on kidney cellular landscape using single-cell RNA sequencing. Differential gene expression profiles were observed in proximal tubules, between the sexes. Interestingly, the SLC22 family of anion transporters, including SLC22A6 and SLC22A8, had different expression profiles between male and female proximal tubule clusters but not sex-dependent abundance at the protein level. Moreover, in different species, we revealed a shared and species-specific differential gene expression between human and mouse kidney proximal tubules. Taken together, at single-cell resolution, this transcriptomic map represents a baseline description of gender biased genes in human kidney proximal tubules, which provide important insights for further studies of physiological differences in kidney.

Keywords: Cellular characteristic; Differences; Gender biased genes; Proximal tubules; scRNA-seq.

MeSH terms

  • Animals
  • Female
  • Humans
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organic Anion Transport Protein 1 / genetics
  • Organic Anion Transport Protein 1 / metabolism
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism
  • Sequence Analysis, RNA / methods
  • Sex Factors*
  • Single-Cell Analysis / methods
  • Transcriptome / genetics

Substances

  • Organic Anion Transport Protein 1
  • Organic Anion Transporters, Sodium-Independent
  • organic anion transport protein 3