Marella Sahiti, Bogle Rachael, Fox Jennifer, Tsoi Lam C, Xing Xianying, Gu Yiqian, Kirma Joseph, Sarkar Mrinal K, van Drongelen Vincent, Klein Benjamin, Kozlow Jeff H, Harms Paul W, Gallagher Katherine, Naik Shruti, Rebecca Vito W, Andersen Bogi, Nakamura Mio, Kahlenberg J Michelle, Modlin Robert L, Billi Allison C, Gudjonsson Johann E
Department of Dermatology, University of Michigan, Ann Arbor, MI, United States.
Department of Computation Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States.
bioRxiv. 2025 May 15:2025.05.10.653184. doi: 10.1101/2025.05.10.653184.
Human skin is not a uniform organ but a mosaic of anatomically distinct niches, with each site finely tuned to unique environmental demands and immune pressures. Yet, the molecular determinants that define these regional identities and their relationship to site-specific vulnerability to inflammatory disease remain poorly understood. Here, we generate a high-resolution single-cell atlas of human skin, profiling 274,834 cells from 96 healthy samples across 7 anatomically distinct sites (acral, arm, axilla, back, face, leg and scalp). Our analysis reveals striking region-specific transcriptional and cellular networks, uncovering how local immune-stromal crosstalk governs tissue homeostasis and underpins anatomical susceptibility to distinct inflammatory diseases such as such as systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis. These findings illuminate the tissue-intrinsic foundations of regional immune identity and provide a blueprint/resource for the development of precision therapies tailored to the distinct immunological microenvironments of specific anatomical skin sites.
人类皮肤并非一个均匀的器官，而是由解剖学上不同的微环境组成的镶嵌体，每个部位都经过精细调节以适应独特的环境需求和免疫压力。然而，定义这些区域特征的分子决定因素以及它们与特定部位对炎症性疾病易感性的关系仍知之甚少。在此，我们生成了一份人类皮肤的高分辨率单细胞图谱，对来自7个解剖学上不同部位（手足、手臂、腋窝、背部、面部、腿部和头皮）的96个健康样本中的274,834个细胞进行了分析。我们的分析揭示了显著的区域特异性转录和细胞网络，揭示了局部免疫-基质相互作用如何控制组织稳态，并支撑了对不同炎症性疾病（如系统性红斑狼疮（SLE）、特应性皮炎（AD）和银屑病）的解剖学易感性。这些发现阐明了区域免疫特征的组织内在基础，并为开发针对特定解剖学皮肤部位独特免疫微环境的精准疗法提供了蓝图/资源。
