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RESEARCH PAPER / 2025-08-25

High-Resolution Spatial Transcriptomics Unveils Spatially Resolved Gene Modules and Fatty Acid Metabolism Dysregulation in Human Skin Aging.

Yin Li, Wenwan Zhang, Yao Teng, Xia Zhang, Sweelin Chew, Yang Liu, Peng Hua, Tingting Yu, Yuao Yan, Yu Bu, Yidan Sun, Luwen Xu, Qiaoyu Fu, Lifang Lei, Yining Chen, Zhengcheng Liu, Caibing Wang, Peiying Zhu, Yao Yu, Nan Huang, Qingfeng Li, Caiyue Liu, Liang Zhang

Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. · pubmed

Abstract

Human skin aging involves intricate micrometer-scale changes in cellular organization. High-resolution spatial transcriptomic analysis is crucial for deciphering the complex interplay of cell types and molecular processes underlying skin aging. In this study, the spatially enhanced-resolution omics-sequencing technique was employed to generate a high-resolution spatial transcriptomic atlas of human eyelid skin, capturing age-related alterations in gene expression. Integrating this atlas with multiplexed FISH, we spatially mapped known cell populations, identified 8 spatial tissue clusters, and uncovered 18 spatially correlated gene modules in human skin. Our analysis revealed that human eyelid skin aging is characterized not only by dermal atrophy and chronic inflammation but also by reduced dermal-epidermal communication, decreased epidermal fatty acid synthesis, potential loss of epidermal cell identity, and diminished c-FOS expression in the epidermis. Functional studies using primary human keratinocytes and a reconstructed full-thickness skin model (T-Skin

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that human eyelid skin aging is characterized by reduced dermal-epidermal communication and dysregulation of fatty acid metabolism. This research is relevant as it explores the molecular processes underlying skin aging, which can contribute to a better understanding of the biological mechanisms of aging and potential interventions.

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