■代谢稳态的差异,糖尿病,男性和女性之间的肥胖在啮齿动物和人类中很明显。迷走神经神经节中的迷走神经感觉神经元支配各种内脏器官,并使用专门的神经末梢来感知感觉信号。这个内脏器官-脑轴在将相互感觉信号传递到更高的大脑中心中起作用,以及调节迷走神经反射。我假设迷走神经感觉神经元的分子不同群体将在导致两性之间代谢稳态的差异中发挥作用。
■使用10X基因组学铬平台对来自迷走神经节的解离细胞进行SnRNA-Seq。
■来自雌性和雄性小鼠的迷走神经感觉神经元的单核RNA测序分析揭示了迷走神经神经节中细胞转录谱的差异。这些差异与性别特异性基因的表达有关,例如Xist,Tsix,Ddx3y在13个神经元集群中,雄性小鼠中四分之一的神经元位于富含Ddx3y的VN1和VN8簇中,显示出更高的Trpv1,Piezo2,Htr3a,和Vip基因。相比之下,在Xist富集簇VN4、6、7、10、11和13中发现了70%的雌性神经元,这些簇显示出富集的基因,例如Fgfr1,Lpar1,Cpe,Esr1,Nrg1,Egfr,Oprm1确定了两个卫星细胞簇,其中一种在雄性小鼠中含有少突胶质细胞前体细胞。少量细胞表达Ucp1和Plin1,表明它们是神经外缘脂肪细胞。
■了解迷走神经感觉神经元中不同转录组特征对能量平衡和代谢稳态的生理意义将有助于开发针对肥胖和代谢失调的性别特异性治疗方法。
UNASSIGNED: Differences in metabolic homeostasis, diabetes, and obesity between males and females are evident in rodents and humans. Vagal sensory neurons in the
vagus nerve ganglia innervate a variety of visceral organs and use specialized nerve endings to sense interoceptive signals. This visceral organ-brain axis plays a role in relaying interoceptive signals to higher brain centers, as well as in regulating the vago-vagal reflex. I hypothesized that molecularly distinct populations of vagal sensory neurons would play a role in causing differences in metabolic homeostasis between the sexes.
UNASSIGNED: SnRNA-Seq was conducted on dissociated cells from the
vagus nerve ganglia using the 10X Genomics Chromium platform.
UNASSIGNED: Single-nucleus RNA sequencing analysis of vagal sensory neurons from female and male mice revealed differences in the transcriptional profiles of cells in the
vagus nerve ganglia. These differences are linked to the expression of sex-specific genes such as Xist, Tsix, and Ddx3y. Among the 13 neuronal clusters, one-fourth of the neurons in male mice were located in the Ddx3y-enriched VN1 and VN8 clusters, which displayed higher enrichment of Trpv1, Piezo2, Htr3a, and Vip genes. In contrast, 70% of the neurons in females were found in Xist-enriched clusters VN4, 6, 7, 10, 11, and 13, which showed enriched genes such as Fgfr1, Lpar1, Cpe, Esr1, Nrg1, Egfr, and Oprm1. Two clusters of satellite cells were identified, one of which contained oligodendrocyte precursor cells in male mice. A small population of cells expressed Ucp1 and Plin1, indicating that they are epineural adipocytes.
UNASSIGNED: Understanding the physiological implications of distinct transcriptomic profiles in vagal sensory neurons on energy balance and metabolic homeostasis would help develop sex-specific treatments for obesity and metabolic dysregulation.