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Tissue mosaicism following stem cell aging: blood as an exemplar

Nature Aging volume 4, pages 295–308 (2024)Cite this article

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Abstract

Loss of stem cell regenerative potential underlies aging of all tissues. Somatic mosaicism, the emergence of cellular patchworks within tissues, increases with age and has been observed in every organ yet examined. In the hematopoietic system, as in most tissues, stem cell aging through a variety of mechanisms occurs in lockstep with the emergence of somatic mosaicism. Here, we draw on insights from aging hematopoiesis to illustrate fundamental principles of stem cell aging and somatic mosaicism. We describe the generalizable changes intrinsic to aged stem cells and their milieu that provide the backdrop for somatic mosaicism to emerge. We discuss genetic and nongenetic mechanisms that can result in tissue somatic mosaicism and existing methodologies to detect such clonal outgrowths. Finally, we propose potential avenues to modify mosaicism during aging, with the ultimate aim of increasing tissue resiliency.

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Fig. 1: Stem cell aging occurs in lockstep with blood somatic mosaicism.
Fig. 2: Drivers of somatic mosaicism in healthy and diseased tissue.
Fig. 3: Methodologies for detection of somatic mosaicism.
Fig. 4: Somatic mosaicism during stem cell aging and potential strategies to restore clonal diversity.

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Acknowledgements

We thank members of the Goodell laboratory for their constructive discussions. C.D.K. was supported by a National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases fellowship training grant (1F30DK131638-01A1). The Goodell laboratory is supported by grants from the National Institutes of Health, including AG036695, CA183252, CA237291, DK092883 and CA265748 and the Milky Way Research Foundation.

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  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    Chiraag D. Kapadia & Margaret A. Goodell

  2. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    Chiraag D. Kapadia & Margaret A. Goodell

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C.D.K. and M.A.G. wrote the manuscript and prepared the figures.

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Kapadia, C.D., Goodell, M.A. Tissue mosaicism following stem cell aging: blood as an exemplar. Nat Aging 4, 295–308 (2024). https://doi.org/10.1038/s43587-024-00589-0

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