猕猴下丘脑对肥胖和糖尿病的特定区域转录组反应

Ying Lei, Xian Liang, Yunong Sun, Ting Yao, Hongyu Gong, Zhenhua Chen, Yuanqing Gao, Hui Wang, Ru Wang, Yunqi Huang, Tao Yang, Miao Yu, Longqi Liu, Chun-Xia Yi, Qing-Feng Wu, Xingxing Kong, Xun Xu, Shiping Liu, Zhi Zhang, Tiemin Liu
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引用次数: 0

摘要

下丘脑在肥胖和糖尿病的发展过程中起着至关重要的作用;然而,其结构的复杂性和细胞的异质性阻碍了靶向治疗。在这里,我们分析了肥胖猕猴和散发性2型糖尿病猕猴下丘脑的单细胞和空间转录组,揭示了簇和基因的灵长类特异性分布以及空间区域、细胞类型和基因特征的特异性变化。绒毛膜下核(INF)和室旁核(PVN)最容易受到代谢紊乱的影响,而室旁核对糖尿病更为敏感。在 INF 中,肥胖会导致突触可塑性和能量感应能力降低,而糖尿病则会导致分子重编程,这与澹细胞屏障受损、小胶质细胞活化和神经元炎症反应有关。在PVN中,糖尿病猕猴的细胞代谢和神经活动受到抑制。空间转录组数据显示,在糖尿病患者中,小胶质细胞更喜欢第三脑室的实质组织。我们的研究结果提供了一个与肥胖和糖尿病相关的分子变化的全面视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.

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