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single-cell transcriptomic profiling of the hypothalamic median eminence during aging

Journal of Genetics and Genomics 2022年第6期49卷 523-536页

作者： Zhen-Hua Chen Si Li Mingrui Xu Candace CLiu Hongying Ye Ben Wang Qing-Feng Wu State Key Laboratory of Molecular Development Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Department of Pathology Stanford University School of MedicineStanfordCA 94305USA Department of Endocrinology and Metabolism Huashan HospitalFudan UniversityShanghai 200040China Department of Obstetrics and Gynecology Baoding Second Central HospitalBaodingHebei 072750China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesBeijing 100101China Chinese Institute for Brain Research Beijing 102206China Beijing Children’s Hospital Capital Medical UniversityBeijing 100045China

Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrine systems,may impair hormone release,energy homeostasis,and central sensing of circulating molecules,leading to systemic and reproductive aging.However,the molecular and cellular features of ME aging remain largely unknown.Here,we describe the transcriptional landscape of young and middleaged mouse ME at single-cell resolution,revealing the common and cell type-specific transcriptional changes with age.The transcriptional changes in cell-intrinsic programs,cell-cell crosstalk,and cellextrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular,signaling,and molecular levels.Importantly,our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome.Together,our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process,which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.

关键词： Hypothalamic median eminence Single-cell transcriptomic analysis Vascular and leptomeningeal cells Aging

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