Beiersdorf AG, Research and Development, Troplowitzstraße 17, 22529, Hamburg, Germany.
Institute for Bioinformatics, University Medicine Greifswald, Greifswald, Germany.
Sci Rep. 2020 Jul 31;10(1):12918. doi: 10.1038/s41598-020-69683-8.
The simultaneous analysis of different regulatory levels of biological phenomena by means of multi-omics data integration has proven an invaluable tool in modern precision medicine, yet many processes ultimately paving the way towards disease manifestation remain elusive and have not been studied in this regard. Here we investigated the early molecular events following repetitive UV irradiation of in vivo healthy human skin in depth on transcriptomic and epigenetic level. Our results provide first hints towards an immediate acquisition of epigenetic memories related to aging and cancer and demonstrate significantly correlated epigenetic and transcriptomic responses to irradiation stress. The data allowed the precise prediction of inter-individual UV sensitivity, and molecular subtyping on the integrated post-irradiation multi-omics data established the existence of three latent molecular phototypes. Importantly, further analysis suggested a form of melanin-independent DNA damage protection in subjects with higher innate UV resilience. This work establishes a high-resolution molecular landscape of the acute epidermal UV response and demonstrates the potential of integrative analyses to untangle complex and heterogeneous biological responses.
通过多组学数据整合对生物现象的不同调控水平进行同步分析已被证明是现代精准医学中一种非常有价值的工具，但许多最终导致疾病表现的过程仍难以捉摸，尚未在这方面进行研究。在这里，我们深入研究了体内健康人类皮肤在重复紫外线照射后的转录组学和表观遗传学水平上的早期分子事件。我们的结果首次提示了与衰老和癌症相关的表观遗传记忆的即刻获得，并证明了对辐照应激的表观遗传和转录组学反应具有显著相关性。这些数据可以精确预测个体间的紫外线敏感性，并在整合了辐照后的多组学数据上进行分子亚型分类，确定了三种潜在的分子光型。重要的是，进一步的分析表明，在具有较高内在紫外线抵抗力的受试者中存在一种黑色素非依赖性的 DNA 损伤保护形式。这项工作建立了急性表皮紫外线反应的高分辨率分子图谱，并证明了整合分析的潜力，可以阐明复杂和异质的生物学反应。
