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
Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
iScience. 2024 Sep 12;27(10):110908. doi: 10.1016/j.isci.2024.110908. eCollection 2024 Oct 18.
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. quiescence assays demonstrate that PD-L1 expression is a physiological attribute of quiescence in this cell lineage and reinforces this cell state. , 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.
细胞静止是一种可逆且受到严格调控的干细胞功能，对健康衰老至关重要。然而，衰老过程中控制静止的因素仍不清楚。利用黑素细胞干细胞（McSCs），我们发现干细胞静止既不是被动的也不是静态的。例如，从增殖的成黑素细胞向静止的黑素细胞干细胞转变的基因表达谱分析揭示了免疫检查点蛋白PD-L1的组织特异性调控。静止分析表明，PD-L1表达是该细胞谱系中静止的一种生理属性，并强化了这种细胞状态。静止的McSCs的一个子集以PD-L1为特征。虽然McSCs的总数随着年龄的增长而减少，但PD-L1+ McSCs似乎对耗竭具有抗性。这种现象与表现出更深层次转录组静止的衰老McSC库一致。我们预测，随着年龄增长而保留的静止PD-L1+干细胞可能作为重新激活的细胞靶点。
