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

Yoshiharu Muto, Parker C. Wilson, Nicolas Ledru, Haojia Wu, Henrik Dimke, Sushrut S. Waikar, Benjamin D. Humphreys

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish
Article number2190
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

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