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Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury

ABSTRACT: Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury

PROVIDER: PRJNA612350 | ENA |

REPOSITORIES: ENA

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Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury

Project description:Background: The kidney glomerulus is a specialized capillary bed that is involved in urine production and blood pressure control. Glomerular injury is a major cause of chronic kidney disease, a widespread epidemic without therapeutic options. Single-cell transcriptomics have radically improved our ability to characterize complex organs, such as the kidney. Cells of the glomerulus, however, have been largely underrepresented in previous single cell kidney studies due to their paucity and intractability. Methods: We used single-cell RNA sequencing to comprehensively characterize the different types of cells in the glomerulus from healthy mice and from four different disease models (nephrotoxic serum nephritis, diabetes, doxorubicin toxicity, CD2AP deficiency). Results: All cell types in the glomerulus were identified using unsupervised clustering analysis. We identified novel marker genes and gene signatures of mesangial cells, vascular smooth muscle cells of the afferent and efferent arteriole, parietal epithelial cells, and three different types of endothelial cells. Analysis of the disease models revealed cell type-specific and injury type-specific responses in the glomerulus, including acute activation of the Hippo pathway in podocytes after nephrotoxic immune injury. Conclusions: We have generated a comprehensive high-resolution single-cell transcriptomic profile of the kidney glomerulus from healthy and injured mice. The dataset provides a useful resource for identifying novel disease-related genes and pathways.

2020-07-13 | GSE146912 | GEO

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Project description: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), were missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we used Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis revealed genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells (MDCs). Importantly, we detected 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 observed 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.

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