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Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes
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Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes
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Journal Article
Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes
2021
Overview
Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), are missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we use Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis reveals genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells. Importantly, we detect heterogeneity in glomerulus-associated
Pdgfrb
-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observe remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.
The molecular identity of renal glomerular cells is poorly characterized and rodent glomerulopathy models translate poorly to humans. Here, the authors show molecular signatures of glomerulus-associated cells using single cell RNA sequencing and highlight differences between mouse and human cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 38
/ 38/91
/ 45
/ 45/91
/ 64
/ 64/60
/ 692/308
/ 692/4017
/ Animals
/ Endothelial Cells - metabolism
/ Glomerular Mesangium - cytology
/ Glomerular Mesangium - metabolism
/ Humanities and Social Sciences
/ Humans
/ Kidneys
/ Male
/ Mice
/ Protein Biosynthesis - genetics
/ Receptor, Platelet-Derived Growth Factor beta - genetics
/ Receptors, Phospholipase A2 - genetics
/ RNA
/ RNA-Seq
/ Science
