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Cellular plasticity in kidney injury and repair

Nature Reviews Nephrology volume 13, pages 39–46 (2017)Cite this article

Subjects

Key Points

  • The ability of a mature cell to convert into a different cell type is called cell plasticity

  • Originally described in cultured cells, cell plasticity is now a recognized feature of organisms, particularly in response to injury

  • Epithelial dedifferentiation occurs after kidney injury, and can be considered as a limited form of cellular plasticity

  • No evidence exists to support the notion that epithelial dedifferentiation confers multipotency, or the ability of a cell from one tubule segment to differentiate into a cell from another segment

  • The potential existence of a fixed population of epithelial progenitors versus the existence of cells with universal dedifferentiation capacity is still controversial

  • The molecular pathways underlying epithelial cell plasticity are likely to be different from developmental pathways, and must be understood in order to identify novel therapeutic targets

Abstract

Terminally differentiated cells can be reprogrammed to pluripotency or directly to another differentiated cell type in vitro, a capacity termed cellular plasticity. Plasticity is not limited to in vitro manipulations but rather represents an important aspect of the regenerative response to injury in organs. Differentiated adult cells retain the capacity to dedifferentiate, adopting a progenitor-like phenotype after injury or, alternatively, to transdifferentiate, directly converting to a different mature cell type. Emerging concepts on cellular plasticity have relevance to our understanding of repair after kidney injury, including epithelial regeneration. Here we discuss work published in the past 5 years on the cellular hierarchies and mechanisms underlying kidney injury and repair, with a particular focus on potential roles for cellular plasticity in this response.

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Figure 1: Dedifferentiation: a regenerative response to kidney injury.
Figure 2: Tubular regeneration by dedifferentiation.
Figure 3: Tubular regeneration mediated by scattered progenitor epithelial cells.
Figure 4: Nephron progenitors are unipotent and have segment-restricted progeny.

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Acknowledgements

This work was supported by the NIH/NIDDK DK107274, DK103740 and DK103050 and by an Established Investigator Award of the American Heart Association (to B.D.H.), and by F32 DK103441 (to M.C.-P.).

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine, 660 S. Euclid Avenue, CB 8126, Saint Louis, 63110, Missouri, USA

    Monica Chang-Panesso & Benjamin D. Humphreys

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  1. Monica Chang-Panesso
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  2. Benjamin D. Humphreys
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Contributions

M.C-P and B.D.H. researched the data for the article, contributed equally to discussions of the content, wrote the article and reviewed or edited the manuscript before submission.

Corresponding author

Correspondence to Benjamin D. Humphreys.

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PowerPoint slides

Glossary

Cell plasticity

Ability of a mature cell to convert to a different cell type; dedifferentiation and transdifferentiation are two examples of cell plasticity.

Blastema

Mass of undifferentiated cells that can develop into an organ or body part during embryogenesis, or regenerate an organ or body part after injury in an adult.

Gastric chief cells

Differentiated epithelial cells located deep in the mucosal layer of the stomach lining that secretes pepsinogen and gastric lipase.

Secretory cells

Cells present in the lumen of airways that have both secretory and detoxifying functions. Secretory cells can also differentiate into ciliated airway cells that propel mucus up the airway.

Basal cells

Self-renewing airway stem cells that can differentiate into multiple epithelial cell types.

Mesenchymal cells

Cells that develop in the lymphatic and circulatory systems and connective tissues, including bone and cartilage. Many mesenchymal cells have stem and progenitor cell characteristics such as the ability to differentiate into bone, cartilage or fat.

Label retaining cells

(LRCs). Cells with a slow cell cycle, a property shared by many stem cells. The assay to identify them involves a DNA-analogue pulse, followed by a chase period. Slow-cycling cells retain the DNA label whereas fast-cycling cells dilute it during the chase period.

Rainbow reporter mice

Transgenic mice that express a fluorescent reporter system that enables the genetic labelling of individual cells with each cell expressing a different reporter colour stochastically. This technique enables researchers to distinguish adjacent cells according to the colour of their fluorescent reporter and follow their expansion and fate clonally.

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Chang-Panesso, M., Humphreys, B. Cellular plasticity in kidney injury and repair. Nat Rev Nephrol 13, 39–46 (2017). https://doi.org/10.1038/nrneph.2016.169

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