Quiescence and aging of melanocyte stem cells and a novel association with programmed death-ligand 1

• Published in: iScience Vol. 27; no. 10; p. 110908
• Main Authors: Palmer, Joseph W., Villavicencio, Kyrene M., Idris, Misgana, Baranyk, Ian J., Polycarp, Nunaya, Dawson, Alex D., Weddle, Dominique, Pavan, William J., Filipp, Fabian V., Harris, Melissa L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-10-2024; Elsevier
• Subjects: Functional aspects of cell biology; Stem cells research; Functional aspects of cell biology; Stem cells research
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110908

Cellular quiescence is a reversible and tightly regulated stem cell function essential for healthy aging. However, the elements that control quiescence during aging remain poorly defined. Using melanocyte stem cells (McSCs), we find that stem cell quiescence is neither passive nor static. For example, gene expression profiling of the transition from proliferating melanoblasts to quiescent melanocyte stem cells reveals tissue-specific regulation of the immune checkpoint protein PD-L1. In vitro, quiescence assays demonstrate that PD-L1 expression is a physiological attribute of quiescence in this cell lineage and reinforces this cell state. In vivo, a subset of quiescent McSCs is marked by PD-L1. While the overall number of McSCs decreases with age, PD-L1+ McSCs appear resistant to depletion. This phenomenon coincides with an aged McSC pool that exhibits a deeper transcriptomic quiescence. We predict that quiescent PD-L1+ stem cells retained with age may serve as cellular targets for reactivation.
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•Melanocyte stem cells (McSCs) actively maintain quiescence•Aged McSCs show an enhanced quiescent but not senescent transcriptome•PD-L1 marks some quiescent McSCs and inhibits proliferation in cell models•PD-L1+ McSCs that persist with age may be good targets for reactivation
Stem cells research; Functional aspects of cell biology