Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92627, USA.
School of Mathematics and Statistics, Wuhan University, Wuhan 430072, China; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA.
Cell Rep. 2022 Aug 2;40(5):111155. doi: 10.1016/j.celrep.2022.111155.
Delayed and often impaired wound healing in the elderly presents major medical and socioeconomic challenges. A comprehensive understanding of the cellular/molecular changes that shape complex cell-cell communications in aged skin wounds is lacking. Here, we use single-cell RNA sequencing to define the epithelial, fibroblast, immune cell types, and encompassing heterogeneities in young and aged skin during homeostasis and identify major changes in cell compositions, kinetics, and molecular profiles during wound healing. Our comparative study uncovers a more pronounced inflammatory phenotype in aged skin wounds, featuring neutrophil persistence and higher abundance of an inflammatory/glycolytic Arg1 macrophage subset that is more likely to signal to fibroblasts via interleukin (IL)-1 than in young counterparts. We predict systems-level differences in the number, strength, route, and signaling mediators of putative cell-cell communications in young and aged skin wounds. Our study exposes numerous cellular/molecular targets for functional interrogation and provides a hypothesis-generating resource for future wound healing studies.
老年人的伤口愈合延迟且常常受损，这带来了重大的医学和社会经济挑战。我们对塑造老年皮肤伤口中复杂细胞间通讯的细胞/分子变化还缺乏全面的了解。在这里，我们使用单细胞 RNA 测序来定义年轻和老年皮肤在稳态下的上皮细胞、成纤维细胞、免疫细胞类型和包含的异质性，并在伤口愈合过程中确定细胞组成、动力学和分子特征的主要变化。我们的比较研究揭示了老年皮肤伤口中更明显的炎症表型，其特征是中性粒细胞持续存在，以及更丰富的炎症/糖酵解 Arg1 巨噬细胞亚群，这些巨噬细胞更有可能通过白细胞介素 (IL)-1 向成纤维细胞发出信号，而不是向年轻皮肤伤口中的信号。我们预测了年轻和老年皮肤伤口中潜在细胞间通讯的数量、强度、途径和信号介质的系统水平差异。我们的研究揭示了许多细胞/分子靶标，可用于功能研究，并为未来的伤口愈合研究提供了产生假说的资源。
