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

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-kappa B 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. Single cell transcriptomic and epigenomic sequencing of human kidney highlight diverse cell types and states. These findings help characterize a novel population of injured proximal tubule cells and illustrate the power of multi-omic approaches to characterizing human tissue.

Automated summary

The integration of single cell transcriptome and chromatin accessibility datasets provides deeper insights into cell heterogeneity, demonstrating the potential of single nucleus ATAC-seq in the identification of cell identity and functional heterogeneity. Differentially accessible chromatin regions in promoters associated with differentially expressed genes suggest the involvement of transcription factors like NF-kappa B in driving transitions between cell subpopulations within the kidney. This multi-omics approach improves the detection of unique cell states and redefines cellular heterogeneity in specific regions of the kidney.