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Single cell analysis of the aging hypothalamus

View ORCID ProfileKaitlyn H. Hajdarovic, View ORCID ProfileDoudou Yu, View ORCID ProfileLexi-Amber Hassell, Shane Evans, View ORCID ProfileNicola Neretti, View ORCID ProfileAshley E. Webb
doi: https://doi.org/10.1101/2021.03.07.434282
Kaitlyn H. Hajdarovic
1Graduate program in Neuroscience, Brown University, Providence, RI, 02912, USA
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Doudou Yu
2Graduate program in Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
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Lexi-Amber Hassell
3Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
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Shane Evans
4Graduate program in Computational Biology, Brown University, Providence, RI, 02912, USA
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Nicola Neretti
3Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
5Center on the Biology of Aging, Brown University, Providence, RI 02912, USA
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Ashley E. Webb
3Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
5Center on the Biology of Aging, Brown University, Providence, RI 02912, USA
6Carney Institute for Brain Science, Brown University, Providence, RI 02912, USA
7Center for Translational Neuroscience, Brown University, Providence, RI 02912, USA
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  • For correspondence: Ashley_Webb@brown.edu
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ABSTRACT

Alterations in metabolism, sleep patterns, body composition, and hormone status are all key features of aging. The hypothalamus is a well-conserved brain region that controls these homeostatic and survival-related behaviors. Despite the importance of this brain region in healthy aging, little is known about the intrinsic features of hypothalamic aging. Here, we utilize single nuclei RNA-sequencing to assess the transcriptomes of 22,718 hypothalamic nuclei from young and aged female mice. We identify cell type-specific signatures of aging in neurons, astrocytes, and microglia, as well as among the diverse collection of neuronal subtypes in this region. We uncover key changes in cell types critical for metabolic regulation and body composition, as well as in an area of the hypothalamus linked to cognition. In addition, our analysis reveals female-specific changes in sex chromosome regulation in the aging brain. This study identifies critical cell-specific features of the aging hypothalamus in mammals.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 08, 2021.
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Single cell analysis of the aging hypothalamus
Kaitlyn H. Hajdarovic, Doudou Yu, Lexi-Amber Hassell, Shane Evans, Nicola Neretti, Ashley E. Webb
bioRxiv 2021.03.07.434282; doi: https://doi.org/10.1101/2021.03.07.434282
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Single cell analysis of the aging hypothalamus
Kaitlyn H. Hajdarovic, Doudou Yu, Lexi-Amber Hassell, Shane Evans, Nicola Neretti, Ashley E. Webb
bioRxiv 2021.03.07.434282; doi: https://doi.org/10.1101/2021.03.07.434282

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