Year in Review | Published:

NEW TECHNOLOGIES IN NEPHROLOGY IN 2018

Single-cell genomics and gene editing: implications for nephrology

Nature Reviews Nephrologyvolume 15pages6364 (2019) | Download Citation

Discoveries in 2018 using single-cell sequencing and gene-editing technologies have revealed their transformative potential for the investigation of kidney physiology and disease. Their promise is matched by the speed of their evolution.

Key advances

  • Massively parallel single-cell RNA sequencing (scRNA-seq) enables molecular characterization of cell types and states with unprecedented precision and is having a profound impact across biology2,3,4.

  • Integration of scRNA-seq and genome-wide association study (GWAS) data sets allows for sensitive identification of causal cell types and genes in human kidney disease3,4.

  • Advances in CRISPR–Cas9 gene editing have facilitated the development of new approaches to activate the expression of protective gene programmes in kidney disease models, providing an encouraging proof of principle for this therapeutic approach8,10.

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References

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    Wu, H. & Humphreys, B. D. The promise of single-cell RNA sequencing for kidney disease investigation. Kidney Int. 92, 1334–1342 (2017).

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    Young, M. D. et al. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors. Science 361, 594–599 (2018).

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    Qiu, C. et al. Renal compartment-specific genetic variation analyses identify new pathways in chronic kidney disease. Nat. Med. 24, 1721–1731 (2018).

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    Gillies, C. E. et al. An eQTL landscape of kidney tissue in human nephrotic syndrome. Am. J. Hum. Genet. 103, 232–244 (2018).

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    Park, J. et al. Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science 360, 758–763 (2018).

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    Wu, H. et al. Comparative analysis and refinement of human psc-derived kidney organoid differentiation with single-cell transcriptomics. Cell Stem Cell https://doi.org/10.1016/j.stem.2018.10.010 (2018).

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    Miyagi, A., Lu, A. & Humphreys, B. D. Gene editing: powerful new tools for nephrology research and therapy. J. Am. Soc. Nephrol. 27, 2940–2947 (2016).

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    Xu, X. et al. High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis. Nat. Commun. 9, 3509 (2018).

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    Ikeda, Y. et al. Efficient gene transfer to kidney mesenchymal cells using a synthetic adeno-associated viral vector. J. Am. Soc. Nephrol. 29, 2287–2297 (2018).

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    Liao, H. K. et al. In vivo target gene activation via CRISPR/Cas9-mediated trans-epigenetic modulation. Cell 171, 1495–1507 (2017).

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Author information

Affiliations

  1. Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA

    • Parker C. Wilson
  2. Division of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA

    • Benjamin D. Humphreys
  3. Department of Developmental Biology, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA

    • Benjamin D. Humphreys

Authors

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Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Benjamin D. Humphreys.

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DOI

https://doi.org/10.1038/s41581-018-0094-3

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