Single-cell genomics provide a powerful approach to investigate the intrinsic complexity of the kidney and understand the diverse cell types and states that exist during kidney development, homeostasis and disease. Several advances were made in 2019 that enhance our understanding of kidney immune cell states in health and disease and the quality of current kidney organoid model systems for studying human diseases.
Key advances
Single-cell RNA sequencing (scRNA-seq) has provided a comprehensive census of the immune cell landscape of the kidney, including zonation of immune cells in homeostasis as well as patterns of injury in lupus nephritis1,2,3.
scRNA-seq enabled detailed comparative analysis of podocyte development and maturation in human kidney organoids compared with that of embryonic kidney6.
scRNA-seq has proven a valuable tool with which to assess the reproducibility of human kidney organoids, pinpoint sources of variability and demonstrate that organoid transplantation diminishes off-target cells7.
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References
Stewart, B. J. et al. Spatiotemporal immune zonation of the human kidney. Science 365, 1461–1466 (2019).
Arazi, A. et al. The immune cell landscape in kidneys of patients with lupus nephritis. Nat. Immunol. 20, 902–914 (2019).
Der, E. et al. Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways. Nat. Immunol. 20, 915–927 (2019).
Wilson, P. C. et al. The single-cell transcriptomic landscape of early human diabetic nephropathy. Proc. Natl Acad. Sci. USA 116, 19619–19625 (2019).
Dvela-Levitt, M. et al. Small molecule targets TMED9 and promotes lysosomal degradation to reverse proteinopathy. Cell 178, 521–535.e23 (2019).
Tran, T. et al. In vivo developmental trajectories of human podocyte inform in vitro differentiation of pluripotent stem cell-derived podocytes. Dev. Cell 50, 102–116.e6 (2019).
Subramanian, A. et al. Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation. Nat. Commun. 10, 5462 (2019).
Czerniecki, S. M. et al. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping. Cell Stem Cell 22, 929–940.e4 (2018).
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Clark, A.R., Greka, A. The power of one: advances in single-cell genomics in the kidney. Nat Rev Nephrol 16, 73–74 (2020). https://doi.org/10.1038/s41581-019-0237-1
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DOI: https://doi.org/10.1038/s41581-019-0237-1
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