Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming
Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming
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DOI：
10.1038/s42003-020-0922-4
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发表时间：
2020-04-23
影响因子：
5.9
通讯作者：
Lyko, Frank
中科院分区：
文献类型：
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作者：
Sole-Boldo, Llorenc;Raddatz, Guenter;Lyko, Frank
成纤维细胞是人类皮肤结构和功能所必需的细胞群。虽然成纤维细胞的异质性已经得到了很好的证实，但这种现象还没有得到系统的分析。我们使用单细胞RNA测序分析了来自健康人体捐赠者阳光照射区域的5000多个成纤维细胞的转录本。我们的结果定义了四个可以在空间上定位的主要亚群，并显示了不同的分泌型、间叶型和促炎性功能注释。重要的是，我们发现这种成纤维细胞的‘启动’会随着年龄的增长而减少。我们还表明，衰老导致真皮成纤维细胞与其他皮肤细胞之间的相互作用显著减少，包括真皮-表皮交界处的未分化角质形成细胞。因此，我们的工作为人类真皮成纤维细胞的功能特化提供了证据，并将细胞特性的部分丧失确定为人类真皮中与年龄相关的重要变化。这些发现对理解人类皮肤衰老及其相关表型具有重要意义。Sole-Boldo等人通过单细胞RNA测序表征了未暴露在阳光下的人类皮肤中的真皮成纤维细胞。他们识别成纤维细胞亚群，发现衰老降低了它们的同一性，并预测了它们与其他皮肤细胞的相互作用，从而为皮肤中与年龄相关的变化提供了洞察力。
Fibroblasts are an essential cell population for human skin architecture and function. While fibroblast heterogeneity is well established, this phenomenon has not been analyzed systematically yet. We have used single-cell RNA sequencing to analyze the transcriptomes of more than 5,000 fibroblasts from a sun-protected area in healthy human donors. Our results define four main subpopulations that can be spatially localized and show differential secretory, mesenchymal and pro-inflammatory functional annotations. Importantly, we found that this fibroblast 'priming' becomes reduced with age. We also show that aging causes a substantial reduction in the predicted interactions between dermal fibroblasts and other skin cells, including undifferentiated keratinocytes at the dermal-epidermal junction. Our work thus provides evidence for a functional specialization of human dermal fibroblasts and identifies the partial loss of cellular identity as an important age-related change in the human dermis. These findings have important implications for understanding human skin aging and its associated phenotypes.Sole-Boldo et al characterise dermal fibroblasts in human skin not exposed to sunlight by single-cell RNA sequencing. They identify fibroblast subpopulations and see that aging reduces their identity and predicted interactions with other skin cells, providing insights into age-related changes in skin.