Quiescence and aging of melanocyte stem cells and a novel association with programmed death-ligand 1
Joseph W. Palmer,
Kyrene M. Villavicencio,
Misgana Idris,
Ian J. Baranyk,
Nunaya Polycarp,
Alex D. Dawson,
Dominique Weddle,
William J. Pavan,
Fabian V. Filipp,
Melissa L. Harris
Affiliations
Joseph W. Palmer
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
Kyrene M. Villavicencio
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
Misgana Idris
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
Ian J. Baranyk
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
Nunaya Polycarp
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
Alex D. Dawson
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
Dominique Weddle
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
William J. Pavan
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Fabian V. Filipp
Cancer Systems Biology, Institute of Diabetes and Cancer, Helmholtz Zentrum München, Ingolstädter Landstraβe 1, 85764 München, Germany; School of Life Sciences Weihenstephan, Technical University München, Maximus-von-Imhof-Forum 3, 85354 Freising, Germany; Institute for Advanced Study, Technical University München, Lichtenbergstraße 2a, 85748 München, Germany; Metaflux, San Diego, CA, USA
Melissa L. Harris
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA; Corresponding author
Summary: 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.
