Spatiotemporal single-cell analysis of gene expression in the mouse suprachiasmatic nucleus

Mammalian circadian behaviors are orchestrated by suprachiasmatic nucleus (SCN) in the hypothalamus. Yet basic SCN cell types and their roles in circadian pacemaking are still unclear. In this study, we comprehensively characterized the basic cell types of SCN and their circadian and light-induced gene expression. In SCN, we identified seven major cell types among which neurons, astrocytes, ependymocytes and endothelial cells display cell-type specific circadian gene expression. We found that five SCN neuron subtypes, Avp+/Nms+, Vip+/Nms+, Vip+/Grp+, Cck+/C1ql3+ and Cck+/Bdnf+, differ in their spatial distribution, circadian rhythmicity and light responsiveness. Among the rhythmic neuron subtypes, we observed a wave of circadian gene expression propagating from the subtypes in posterior SCN to the subtypes in anterior SCN. Such wave can be explained by the neuropeptide-receptor signaling network in which Avp+/Nms+ subtype is the leader of circadian oscillations. Our study provides insights into the basic neural mechanism of circadian pacemaking in mammals. Overall design: 10X geomics single cell trascriptome sequencing of mice SCN

哺乳动物的昼夜节律行为由下丘脑视交叉上核（suprachiasmatic nucleus, SCN）调控。然而，SCN的基本细胞类型及其在昼夜节律起搏中的作用仍未明确。本研究对SCN的基本细胞类型，以及其昼夜节律和光诱导基因表达特征进行了全面解析。在SCN中，我们鉴定出7种主要细胞类型，其中神经元、星形胶质细胞、室管膜细胞和内皮细胞呈现出细胞类型特异性的昼夜节律基因表达。我们发现5种SCN神经元亚型，即Avp+/Nms+、Vip+/Nms+、Vip+/Grp+、Cck+/C1ql3+以及Cck+/Bdnf+，在空间分布、昼夜节律性以及光响应性上存在差异。在具有节律性的神经元亚型中，我们观察到昼夜节律基因表达的波从SCN后部的亚型向前部的亚型传播。这种传播波可由神经肽-受体信号网络解释，其中Avp+/Nms+亚型是昼夜节律振荡的主导者。本研究为解析哺乳动物昼夜节律起搏的基本神经机制提供了重要见解。整体实验设计：对小鼠SCN开展10X Genomics单细胞转录组测序。