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Review
. 2022 Jan;18(1):8-21.
doi: 10.1038/s41581-021-00485-5. Epub 2021 Sep 30.

Determining lineage relationships in kidney development and disease

Melissa H Little  1   2   3 , Sara E Howden  4   5 , Kynan T Lawlor  4 , Jessica M Vanslambrouck  4
Affiliations
Review

Determining lineage relationships in kidney development and disease

Melissa H Little et al. Nat Rev Nephrol. 2022 Jan.

Abstract

The lineage relationships of cells provide information about the origins of component cell types during development and repair as well as the source of aberrant cells during disease. Genetic approaches to lineage tracing applied in the mouse have revealed much about how the mammalian kidney forms, including the identification of key progenitors for the nephrons and stromal compartments. Inducible Cre systems have also facilitated lineage tracing studies in the postnatal animal that illustrate the changes in cellular fate that can occur during kidney injury. With the advent of single-cell transcriptional profiling and trajectory analyses, predictions of cellular relationships across development are now being made in model systems, such as the mouse, as well as in human fetal kidney. Importantly, these approaches provide predictions of lineage relationships rather than definitive evidence. Although genetic approaches to the study of lineage have not previously been possible in a human setting, the application of CRISPR-Cas9 gene editing of pluripotent stem cells is beginning to teach us about human lineage relationships.

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References

    1. Kobayashi, A. et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3, 169–181 (2008). This manuscript applied genetic lineage tracing in mice to identify a self-renewing progenitor population within the cap mesenchyme that gives rise to all segments of the epithelial nephron. - PubMed - PMC
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    1. Barker, N. et al. Lgr5+ve stem/progenitor cells contribute to nephron formation during kidney development. Cell Rep. 2, 540–552 (2012). Lineage tracing for Lgr5-derived cells showed the presence of a clonal cellular expansion giving rise to the medial segment of the forming nephron in mouse. - PubMed
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    1. Lazzeri, E. et al. Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury. Nat. Commun. 9, 1344 (2018). Using a combination of Confetti and FUCCI2 lineage tracing mouse models, this study discounted the proliferation of surviving tubular epithelial cells as the predominant reparative mechanism during acute kidney injury, instead demonstrating their hypertrophic response. Tubular repair was found to occur via a distinct subpopulation of Pax2 -expressing epithelial progenitors more resistant to apoptosis and possessing clonogenic capacity. - PubMed - PMC

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