Single-Cell Transcriptomics in Kidney Disease

Single-cell transcriptomics has revolutionised our understanding of kidney biology by resolving the gene expression programmes of individual cells within complex renal tissue. By profiling thousands of cells in parallel, researchers can map the cellular composition and transcriptional states that underpin health, injury and repair in the kidney. This approach has uncovered previously unrecognised subpopulations of tubular epithelial cells, mesangial cells and endothelial cells, and has revealed the molecular cascades driving common pathologies such as diabetic nephropathy, fibrosis and acute kidney injury. Integration of single-cell RNA sequencing with assays of chromatin accessibility and epigenetic modifications has enabled the construction of comprehensive atlases that link regulatory elements to cell-type-specific transcriptional activity. Such atlases not only chart the normal architecture of the nephron but also highlight cell-specific injury responses and repair trajectories. The global significance of this work lies in its capacity to identify precise cellular targets for therapy, to stratify patients by molecular phenotype and to facilitate the development of interventions that modulate disease-driving pathways at single-cell resolution.

Research from Nature Portfolio

Recent studies have produced a spatially anchored epigenomic atlas of the human kidney that integrates single-nucleus RNA and chromatin accessibility profiles across health and injury states. This atlas delineates active, silent and regulatory chromatin regions in distinct nephron segments and identifies cell-type-specific transcription factor networks—such as those centred on ELF3, KLF6 and NR2F1—that govern the transition between homeostasis and injury in proximal tubule and thick ascending limb cells. In diabetic kidney disease, multimodal single-cell sequencing of RNA and ATAC libraries has revealed that proximal tubule injury is accompanied by reduced accessibility of glucocorticoid receptor binding sites and an injury-associated gene expression signature. This work implicates genetic background in shaping the chromatin landscape and suggests that modulation of glucocorticoid receptor activity could mitigate maladaptive transcriptional programmes in the diseased proximal tubule.

Single-Cell Transcriptomics in Kidney Disease publication trend

The graph below shows the total number of articles in single-cell transcriptomics in kidney disease across all publications each year (not limited to Nature Index journals).

Technical terms

Single-cell RNA sequencing: A method to measure gene expression in individual cells, revealing cellular diversity and transcriptional states within tissues.

Single-nucleus ATAC sequencing (snATAC-seq): A technique that profiles chromatin accessibility at single-nucleus resolution, identifying regulatory DNA elements active in each cell type.

Chromatin accessibility: The degree to which DNA is exposed to transcription factors, reflecting regulatory regions that control gene expression.

Mechanosensitive transcriptional pathway: A signalling cascade activated by mechanical stimuli, such as hyperfiltration, that alters gene expression via factors like MRTF and SRF.

mTORC1 signalling: A nutrient- and energy-sensing pathway that regulates cellular metabolism, growth and protein synthesis, often dysregulated in diabetic kidney disease.

References

1. The chromatin landscape of healthy and injured cell types in the human kidney. Nature Communications (2024).
2. Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression. Nature Communications (2022).
3. Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy. Genome Medicine (2023).
4. Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis. Journal of Nanobiotechnology (2024).
5. SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth onset type 2 diabetes. Journal of Clinical Investigation (2023).