A Single-Cell Transcriptomic Atlas of Human Skin Aging. 2021

Zhiran Zou, and Xiao Long, and Qian Zhao, and Yandong Zheng, and Moshi Song, and Shuai Ma, and Yaobin Jing, and Si Wang, and Yifang He, and Concepcion Rodriguez Esteban, and Nanze Yu, and Jiuzuo Huang, and Piu Chan, and Ting Chen, and Juan Carlos Izpisua Belmonte, and Weiqi Zhang, and Jing Qu, and Guang-Hui Liu
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Skin undergoes constant self-renewal, and its functional decline is a visible consequence of aging. Understanding human skin aging requires in-depth knowledge of the molecular and functional properties of various skin cell types. We performed single-cell RNA sequencing of human eyelid skin from healthy individuals across different ages and identified eleven canonical cell types, as well as six subpopulations of basal cells. Further analysis revealed progressive accumulation of photoaging-related changes and increased chronic inflammation with age. Transcriptional factors involved in the developmental process underwent early-onset decline during aging. Furthermore, inhibition of key transcription factors HES1 in fibroblasts and KLF6 in keratinocytes not only compromised cell proliferation, but also increased inflammation and cellular senescence during aging. Lastly, we found that genetic activation of HES1 or pharmacological treatment with quercetin alleviated cellular senescence of dermal fibroblasts. These findings provide a single-cell molecular framework of human skin aging, providing a rich resource for developing therapeutic strategies against aging-related skin disorders.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D004817 Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072056 Transcription Factor HES-1 A basic-helix-loop-helix transcription factor that functions as a transcriptional repressor for genes transcribed by bHLH proteins. For example, it may negatively regulate MYOGENESIS by inhibiting MyoD1 and ASH1 proteins. It is also required for the stability of FANCONI ANEMIA COMPLEMENTATION GROUP PROTEINS and their localization to the cell nucleus in response to DNA DAMAGE. Hairy and Enhancer of Split 1 Protein,Hairy-Like Transcription Factor,HES-1, Transcription Factor,Hairy Like Transcription Factor,Transcription Factor HES 1,Transcription Factor, Hairy-Like
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D015595 Skin Aging The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. Photoaging of Skin,Skin Wrinkling,Solar Aging of Skin,Aging, Skin,Skin Wrinklings,Wrinkling, Skin

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