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Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes

ABSTRACT: 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.

PROVIDER: EGAS00001004943 | EGA |

REPOSITORIES: EGA

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Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes

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.

2020-11-21 | GSE160048 | GEO

Bulk RNA-sequencing of FACS-sorted kidney glomerular cell types from BTBR ob/ob mice and glomeruli isolated from ex vivo perfused kidneys

Project description:To investigate the gene expression levels of major glomerular cell types in BTBR ob/ob mice and in glomeruli under hyperfiltration Bulk RNA-sequencing of glomerular cell types from BTBR ob/ob and BTBR +/+ mice at three time points (6/12/18 weeks). The glomeruli were isolated from ex vivo perfused kidney (hyperfiltration) and unperfused kidney (control) from the mouse.

2022-11-21 | GSE218086 | GEO

A single-cell transcriptome atlas of mouse glomerulus

Project description:Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. As yet, it remains unknown to what extent cellular heterogeneity exists within healthy glomerular cell populations. Here, we used nanodroplet-based, highly parallel transcriptional profiling to characterize the cellular content of purified wildtype mouse glomeruli. Unsupervised clustering of 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells, which can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry stainings obtained from the Human Protein Atlas. Subclustering of glomerular endothelial cells revealed a subset of activated endothelium, expressing marker genes related to endothelial proliferation. Additionally, the podocyte population could be divided in three different subclusters. In conclusion, our study comprehensively characterizes gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease.

2018-04-27 | GSE111107 | GEO

Single-cell profiling of glomerular cells provides a dynamic picture in experimental diabetic kidney disease

Project description:Background: Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into cell-specific gene expression profiles in normal kidneys. However, in diseased kidneys, understanding of changes in specific cells, particularly glomerular cells, remains limited. Methods: To elucidate the glomerular cell–specific gene expression changes in diabetic kidney disease, we performed scRNA-seq analysis of isolated glomerular cells from streptozotocin-induced diabetic endothelial nitric oxide synthase (eNOS)–deficient (eNOS-/-) mice and control eNOS-/- mice. Results: We identified five distinct cell populations, including glomerular endothelial cells, mesangial cells, podocytes, immune cells, and tubular cells. Using scRNA-seq analysis, we confirmed the expression of glomerular cell–specific markers and also identified several new potential markers of glomerular cells. The number of immune cells was significantly higher in diabetic glomeruli compared with control glomeruli, and further cluster analysis showed that these immune cells were predominantly macrophages. Analysis of differential gene expression in endothelial and mesangial cells of diabetic and control mice showed dynamic changes in the pattern of expressed genes, many of which are known to be involved in diabetic kidney disease. Moreover, gene expression analysis showed variable responses of individual cells to diabetic injury. Conclusion: Our findings demonstrate the ability of scRNA-seq analysis in isolated glomerular cells from diabetic and control mice to reveal dynamic changes in gene expression in diabetic kidneys, with variable responses of individual cells. Such changes, which might not be apparent in bulk transcriptomic analysis of glomerular cells, may help identify important pathophysiologic factors contributing to the progression of diabetic kidney disease.

2019-03-08 | GSE127235 | GEO

Tripartite separation of glomerular proteomes from reporter-free mice

Project description:Renal blood filtration occurs in a functional unit called the glomerulus. The resident cell types comprise the filtration barrier, namely podocytes, mesangial cells and glomerular endothelial cells. Here we introduce a glomerular cell isolation protocol, which enables the separation of these three cell types in sufficient amounts and purity to allow detailed protein-biochemical investigations. We demonstrate that the expression of fluorescent transgenes in glomerular cells can result in proteome artifacts. We show that different mouse strains have different glomerular cell type proteomes. Further, we demonstrate the power of the technique to identify new glomerular cell type-enriched proteins and demonstrate the potential of this globally applicable technique in the dissection of cell-specific disease responses and intra-glomerular cell-type crosstalk.

2021-11-12 | PXD024481 | Pride

FACS sorted podocytes, mesangial cells

Project description:FACS sorted glomerular kidney cells from a single mouse were subjected to proteomics.

2022-10-13 | PXD016237 | Pride

The nephrotxin Puromycin aminonucleoside induces injury in kidney organoids differentiated from human urine SIX2-positive stem cell derived induced pluripotent stem cells.

Project description:Kidney diseases including acute kidney injury (AKI) and chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD), are a worldwide health burden. Organ trans-plantation or kidney dialysis are the only effective available therapeutic tools. Therefore, in vitro models of kidney diseases and the development of prospective therapeutic means are highly demanded. Within the kidney, the glomeruli are involved in blood filtration and waste excre-tion, and are easily affected by changing cellular conditions. Puromycin aminonucleoside (PAN) is a nephrotoxin, which can be harnessed for imitating acute glomerular damage and modelling of glomerular disease. For this reason, we generated kidney organoids from three iPSC lines and treated these with PAN in order to induce kidney injury. Morphological observations re-vealed disruption of glomerular and tubular structures within the kidney organoids upon PAN treatment, which were confirmed by transcriptome analyses. Subsequent analyses revealed an upregulation of immune response as well as inflammatory and cell death-related processes. We concluded that treatment of iPSC-derived kidney organoids with PAN induces kidney injury mediated an intertwined network of inflammation, cytoskeletal re-arrangement, DNA damage, apoptosis and cell death. Furthermore, urine stem cell-derived kidney organoids can be used for modelling of kidney-associated diseases and drug discovery.

2022-03-04 | GSE186823 | GEO

Single-cell RNA sequencing reveals mRNA splice isoform switching during kidney development (bulk)

Project description:Kidney development is a complex process involving multiple interacting and transforming cell types. These cell types were recently characterized using the Drop-seq single-cell technology for measuring gene expression from many thousands of individual cells. However, many genes can also be alternatively spliced and this creates an additional layer of cellular heterogeneity that cannot be measured with the Drop-seq technology. This study describes the use of full transcript length single-cell RNA sequencing to characterize alternative splicing in the developing mouse fetal kidney; in particular, the identification of genes that are alternatively spliced during the transition from mesenchymal to epithelial cell states, as well as their splicing regulators. These results improve our understanding of the molecular mechanisms involved in kidney development.

2020-07-27 | GSE147525 | GEO

Single-cell RNA sequencing reveals mRNA splice isoform switching during kidney development

2020-07-27 | GSE146988 | GEO

ena-DATASET-KI-10-01-2021-10:28:44:984-430 - samples

Project description:Smart-seq2 single cell RNA sequencing reads from kidney glomerular single cells of healthy human individuals. The dataset contains single-end fastq files of 766 single cells.

| EGAD00001006861 | EGA

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