Comprehensive Cell Type Specific Transcriptomics of the Human Kidney

Abstract

The human kidney is a complex organ composed of specialized cell types. To better define this cellular complexity, we profiled the individual transcriptomes of 22,469 normal human kidney cells, identifying 27 cell types. We describe three distinct endothelial cell populations, a novel subset of intercalated cells, interstitial macrophage and dendritic cells, and identify numerous novel cell-type-specific markers, many validated using imaging mass cytometry and immunohistochemistry. Receptor-ligand analysis revealed previously unknown intercalated-endothelial and intercalated-distal nephron interactions, suggesting a role in maintenance of vascular integrity and intercalated cell survival. Notably, kidney disease-associated genes were largely expressed in proximal tubules, podocytes, endothelial and myeloid cells, highlighting an underappreciated role for endothelial cells in kidney pathologies. Our analysis also provides a resource of cell type enriched markers, solute carriers, channels and lncRNAs. In summary, this cell-type-specific transcriptome resource provides the foundation for a comprehensive understanding of kidney function and dysfunction at single cell resolution.

Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions

“…22,36 In a single-cell transcriptomic analysis, this subgroup clustered into a distinct group of PECs rather than proximal tubule cells. 37 This is supported by our observation that the PEC-specific transgenic mouse line PEC-rtTA labels intermediate and cuboidal PECs, but not proximal tubule cells, consistent with the notion that these cell populations are not identical. Intermediate PECs have been reported in various mammals based on their morphology (i.e., triangular shape), absence of apical microvilli, and low number of mitochondria.…”

A Functional Landscape of CKD Entities From Public Transcriptomic Data

“…As more data become available, either from micro-arrays or RNA sequencing, these can be integrated in our pipeline. Furthermore, the burgeoning field of scRNAseq has just started to produce data from kidneys 50,51 and can revolutionize our understanding of the functioning of the kidney and its pathologies. 52,53 In particular, scRNA-seq data can provide signatures of the many cell types in the kidney, which in turn can be used to deconvolute the composition of cell types 12 in the more abundant and cost-effective bulk expression data sets.…”

A functional landscape of chronic kidney disease entities from public transcriptomic data

“…As more data sets become available, either from micro-arrays or RNA-seq, these can be integrated in our pipeline. Furthermore, the burgeoning field of single-cell RNA (scRNA) has just started to produce data sets in kidney 36,37 and holds the potential to revolutionize our understanding of the functioning of the kidney and its pathologies 38 39 . In particular, scRNA data can provide signatures of the many cell types of the kidney, which in turn can be used to deconvolute the composition of cell types 12 in the more abundant and cost-effective bulk expression datasets 39 .…”