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Cell senescence

Senescent fibroblasts support lung repair

Nature Reviews Molecular Cell Biology volume 23, page 775 (2022)Cite this article

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The emergence of senescent cells is generally associated with ageing and decline of tissue regeneration. Reyes et al. now show that fibroblasts with cellular senescence properties are present in healthy epithelial tissues and — by upregulating the senescence associated secretory phenotype (SASP) — they support stem-cell function and tissue repair.

A hallmark of cellular senescence is the expression of the cell cycle inhibitor p16INK4a (encoded by Cdkn2a in mice). The authors generated a sensitive, fluorescent reporter of p16INK4a expression, in which several H2B-GFP cassettes were inserted into the Cdkn2a locus. This construct was used to create transgenic mice (called INKBRITE), to visualize p16INK4a-positive cells in vivo. GFP-positive cells were detected in healthy, young (starting shortly after birth) INKBRITE mice. These cells were located at sub-epithelial compartments of barrier tissues, in particular in the lung, but also in the small intestine, colon and skin, which indicates that p16INK4a is not restricted to aged tissues. Most of the cells were immune cells and fibroblasts.

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References

Original article

  • Reyes, N. S. et al. Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung. Science 378, 192–201 (2022)

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Related article

  • di Micco, R. et al. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 22, 75–95 (2021)

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  1. Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/

    Paulina Strzyz

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  1. Paulina Strzyz
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Correspondence to Paulina Strzyz.

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Strzyz, P. Senescent fibroblasts support lung repair. Nat Rev Mol Cell Biol 23, 775 (2022). https://doi.org/10.1038/s41580-022-00559-7

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  • DOI: https://doi.org/10.1038/s41580-022-00559-7

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