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Volume 49 Issue 6
Jun.  2022
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Article Navigation >  Journal of Genetics and Genomics  > 2022  >  49(6): 523-536

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

doi: 10.1016/j.jgg.2022.01.001
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    a. State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;

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    b. University of Chinese Academy of Sciences, Beijing 100101, China;

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    c. Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA;

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    d. Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, China;

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    e. Department of Obstetrics and Gynecology, Baoding Second Central Hospital, Baoding, Hebei 072750, China;

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    f. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing 100101, China;

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    g. Chinese Institute for Brain Research, Beijing 102206, China;

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    h. Beijing Children's Hospital, Capital Medical University, Beijing 100045, China

Funds:

The work was supported by the National Key R&

D Program of China (2019YFA0801900 and 2018YFA0801104), the National Natural Science Foundation of China (31771131, 81891002, 31921002, and 32070972), the Strategic Priority Research Program of Chinese Academy of Sciences (XDB32020000), the Hundred-Talent Program (Chinese Academy of Sciences), the Beijing Municipal Science &

Technology Commission (Z210010 and Z181100001518001), and the Baoding Technical Program (2141ZF027).

  • Received Date: 2021-10-04
  • Accepted Date: 2022-01-03
  • Rev Recd Date: 2021-12-31
  • Publish Date: 2022-06-30
    Abstract
  • 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 middle-aged 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 cell-extrinsic 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.
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