Genome-wide identification of genes essential for podocyte cytoskeletons based on single-cell RNA sequencing

Lu, Yuxin; Ye, Yuting; Bao, Wei; Yang, Qianqian; Wang, Jinquan; Liu, Zhihong; Shi, Shaolin

doi:10.1016/j.kint.2017.04.022

Cited by 74 publications

(92 citation statements)

References 44 publications

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“…They found that deficiency of 30 of the 37 genes resulted in cytoskeletal injury of podocytes, suggesting that most of the 92 candidate genes are truly podocyte-specific essential genes and mainly involved in the maintenance of cytoskeletons for podocyte unique structure. This finding is consistent with the fundamental role of podocytes in the glomerular filtration barrier [73]. Their work based on scRNA-seq has greatly facilitated the identification of genes specifically essential for mesangial cells and podocytes.…”

Section: Current Studies In the Field Of Kidney Research That Used Scsupporting

confidence: 80%

“…Lu et al [72,73] used the Fluidigm C1 platform for single glomerular cell capture, lysis, RNA extraction, as well as cDNA synthesis and amplification in the microfluidic system. They determined the identity of each cell by PCR detection of the markers for podocytes or mesangial cells and then sequenced the cDNA.…”

Section: Current Studies In the Field Of Kidney Research That Used Scmentioning

confidence: 99%

“…They determined the identity of each cell by PCR detection of the markers for podocytes or mesangial cells and then sequenced the cDNA. They found that both mesangial cells and podocytes are extremely heterogeneous in gene expression, with correlation coefficients of 0.20 (mesangial cells) and 0.25 (podocytes), respectively [72,73]. They next identified genes expressed in every single mesangial cell or podocyte examined, and speculated that they are either essential for mesangial cells or podocytes to survive (therefore, being house-keeping genes) or essential for the unique structure and function of the cell types, without which the organism will not survive.…”

Section: Current Studies In the Field Of Kidney Research That Used Scmentioning

confidence: 99%

“…Although the essential genes of mouse mesangial cells and podocytes, including the cell type-specific essential genes that govern the unique structure and function of mesangial cells and podocytes, have been identified by scRNA-seq with a specially designed approach [72,73], similar work will have to be conducted for all renal cell types or subtypes in order to better understand the biology and pathogenesis of the cell types in kidney.…”

Section: Perspectivesmentioning

confidence: 99%

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Understanding the Biology and Pathogenesis of the Kidney by Single-Cell Transcriptomic Analysis

Song

Zhang

et al. 2018

Kidney Dis

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Background: Single-cell RNA-seq (scRNA-seq) has recently emerged as a revolutionary and powerful tool for biomedical research. However, there have been relatively few studies using scRNA-seq in the field of kidney study. Summary: scRNA-seq achieves gene expression profiling at single-cell resolution in contrast with the conventional methods of gene expression profiling, which are based on cell population and give averaged values of gene expression of the cells. Single-cell transcriptomic analysis is crucial because individual cells of the same type are highly heterogeneous in gene expression, which reflects the existence of subpopulations, different cellular states, or molecular dynamics, of the cells, and should be resolved for further insights. In addition, gene expression analysis of tissues or organs that usually comprise multiple cell types or subtypes results in data that are not fully applicable to any given cell type. scRNA-seq is capable of identifying all cell types and subtypes in a tissue, including those that are new or present in small quantity. With these unique capabilities, scRNA-seq has been used to dissect molecular processes in cell differentiation and to trace cell lineages in development. It is also used to analyze the cells in a lesion of disease to identify the cell types and molecular dynamics implicated in the injury. With continuous technical improvement, scRNA-seq has become extremely high throughput and cost effective, making it accessible to all laboratories. In the present review article, we provide an overall review of scRNA-seq concerning its history, improvements, and applications. In addition, we describe the available studies in which scRNA-seq was employed in the field of kidney research. Lastly, we discuss other potential uses of scRNA-seq for kidney research. Key Message: This review article provides general information on scRNA-seq and its various uses. Particularly, we summarize the studies in the field of kidney diseases in which scRNA-seq was used and discuss potential additional uses of scRNA-seq for kidney research.

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Section: Current Studies In the Field Of Kidney Research That Used Scsupporting

confidence: 80%

Section: Current Studies In the Field Of Kidney Research That Used Scmentioning

confidence: 99%

Section: Current Studies In the Field Of Kidney Research That Used Scmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Understanding the Biology and Pathogenesis of the Kidney by Single-Cell Transcriptomic Analysis

Song

Zhang

et al. 2018

Kidney Dis

Self Cite

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“…Sub-cluster 1 (from sub-clustering of initial cluster 4) enrichment in PDZ domain proteins is consistent with a role for these proteins in establishing cell-cell contacts and the slit diaphragm that is characteristic of mature podocytes. Indeed, MAGI2 , PDLIM2 , MPP5 , PARD3B and TJP1 are associated with cytoskeletal and barrier function in podocytes (Ihara et al, 2014; Itoh et al, 2014; Koehler et al, 2016; Lu et al, 2017a; Sistani et al, 2011). …”

Section: Resultsmentioning

confidence: 99%

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney

et al. 2018

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The mammalian kidney develops through reciprocal interactions between the ureteric bud and the metanephric mesenchyme to give rise to the entire collecting system and the nephrons. Most of our knowledge of the developmental regulators driving this process arises from the study of gene expression and functional genetics in mice and other animal models. In order to shed light on human kidney development, we have used single-cell transcriptomics to characterize gene expression in different cell populations, and to study individual cell dynamics and lineage trajectories during development. Single-cell transcriptome analyses of 6414 cells from five individual specimens identified 11 initial clusters of specific renal cell types as defined by their gene expression profile. Further subclustering identifies progenitors, and mature and intermediate stages of differentiation for several renal lineages. Other lineages identified include mesangium, stroma, endothelial and immune cells. Novel markers for these cell types were revealed in the analysis, as were components of key signaling pathways driving renal development in animal models. Altogether, we provide a comprehensive and dynamic gene expression profile of the developing human kidney at the single-cell level.

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Podocyte Pathogenic Bone Morphogenetic Protein‐2 Pathway and Immune Cell Behaviors in Primary Membranous Nephropathy

Cai,

Meng,

Zhou

et al. 2024

Advanced Science

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Primary membranous nephropathy (PMN) is one of the leading causes of end‐stage renal disease, and the most frequent cause of massive proteinuria in nondiabetic adults, resulting in fatal complications. However, the underlying pathomechanisms of PMN remain largely unclear. Here, single‐cell RNA sequencing is employed to analyze kidney biopsies from eleven PMN patients and seven healthy subjects. Profiling 44 060 cells from patients allowed us to characterize the cellular composition and cell‐type‐specific gene expression in the PMN kidney. The complement‐induced BMP2/pSMAD1/COL4 pathway is identified as the pathogenic pathway in podocytes, bridging two key events, i.e., complement system activation and glomerular basement membrane thickening in PMN. Augmented infiltration and activation of myeloid leukocytes and B lymphocytes are found, profiling delicate crosstalk of immune cells in PMN kidneys. Overall, these results provide valuable insights into the roles of podocytes and immune cells in PMN, and comprehensive resources toward the complete understanding of PMN pathophysiology.

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Genome-wide identification of genes essential for podocyte cytoskeletons based on single-cell RNA sequencing

Cited by 74 publications

References 44 publications

Understanding the Biology and Pathogenesis of the Kidney by Single-Cell Transcriptomic Analysis

Understanding the Biology and Pathogenesis of the Kidney by Single-Cell Transcriptomic Analysis

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney

Podocyte Pathogenic Bone Morphogenetic Protein‐2 Pathway and Immune Cell Behaviors in Primary Membranous Nephropathy

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