Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

Nat Commun. 2021 Apr 13;12(1):2190. doi: 10.1038/s41467-021-22368-w.

Abstract

The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NF-κB that promotes VCAM1 expression and drives transition between a subpopulation of proximal tubule epithelial cells. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromatin / genetics*
  • Gene Expression Regulation
  • Genetic Heterogeneity*
  • Hepatocyte Nuclear Factor 4
  • Humans
  • Kidney / metabolism*
  • Middle Aged
  • NF-kappa B
  • Promoter Regions, Genetic
  • RNA, Small Nuclear
  • Transcription Factor AP-2
  • Transcription Factors / metabolism
  • Transcriptome*
  • Transposases
  • Vascular Cell Adhesion Molecule-1

Substances

  • Chromatin
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • NF-kappa B
  • RNA, Small Nuclear
  • TFAP2B protein, human
  • Transcription Factor AP-2
  • Transcription Factors
  • Vascular Cell Adhesion Molecule-1
  • Transposases