Single-cell analysis of the aging female mouse hypothalamus
Single-cell analysis of the aging female mouse hypothalamus
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DOI：
10.1038/s43587-022-00246-4
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发表时间：
2022-07-01
期刊：
影响因子：
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通讯作者：
Webb, Ashley E.
中科院分区：
文献类型：
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作者：
Hajdarovic, Kaitlyn H.;Yu, Doudou;Webb, Ashley E.
新陈代谢、睡眠模式、身体成分和荷尔蒙状态的改变都是衰老的关键特征。虽然下丘脑是一个保存完好的大脑区域，控制着这些动态平衡和与生存相关的行为，但人们对下丘脑衰老的内在特征知之甚少。在这里，我们对40064个来自年轻和老年雌性小鼠的下丘脑细胞核进行了单核RNA测序。我们在神经元亚型以及星形胶质细胞和小胶质细胞中发现了衰老的细胞类型特异性特征。我们发现了对代谢调节和身体成分至关重要的细胞类型的变化，以及与认知有关的下丘脑区域的变化。我们的分析还揭示了下丘脑老化的一个意想不到的女性特有的特征：X失活的主要调节因子Xist随着年龄的增长而升高，特别是在下丘脑神经元中。此外，利用机器学习，我们证明了X染色体基因的水平和Xist本身可以准确地预测细胞年龄。这项研究确定了哺乳动物下丘脑衰老的关键细胞特异性变化，并发现了女性神经元老化的潜在标志。下丘脑控制着代谢和睡眠等与年龄相关的变化等动态平衡功能。在这里，作者对雌性小鼠的年轻和老年下丘脑进行了单核转录组学分析，并描述了基因表达随年龄的变化，特别是X失活基因Xist的表达增加。
Alterations in metabolism, sleep patterns, body composition and hormone status are all key features of aging. While the hypothalamus is a well-conserved brain region that controls these homeostatic and survival-related behaviors, little is known about the intrinsic features of hypothalamic aging. Here, we perform single-nuclei RNA sequencing of 40,064 hypothalamic nuclei from young and aged female mice. We identify cell type-specific signatures of aging in neuronal subtypes as well as astrocytes and microglia. We uncover changes in cell types critical for metabolic regulation and body composition and in an area of the hypothalamus linked to cognition. Our analysis also reveals an unexpected female-specific feature of hypothalamic aging: the master regulator of X inactivation, Xist, is elevated with age, particularly in hypothalamic neurons. Moreover, using machine learning, we show that levels of X chromosome genes and Xist itself, can accurately predict cellular age. This study identifies critical cell-specific changes of the aging hypothalamus in mammals and uncovers a potential marker of neuronal aging in females.The hypothalamus controls homeostatic functions such as metabolism and sleep, which undergo age-related changes. Here the authors perform single-nuclei transcriptomics profiling of young and old hypothalamus from female mice and describe changes in gene expression with age, in particular increased expression of the X inactivation gene Xist.