Single-cell transcriptomics of suprachiasmatic nuclei reveal a Prokineticin-driven circadian network.
Single-cell transcriptomics of suprachiasmatic nuclei reveal a Prokineticin-driven circadian network.
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视交叉上核的单细胞转录组学揭示了前动力素驱动的昼夜节律网络。
DOI：
10.15252/embj.2021108614
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发表时间：
2021-10-18
期刊：
影响因子：
--
通讯作者：
Hastings MH
中科院分区：
文献类型：
--
作者：
Morris EL;Patton AP;Chesham JE;Crisp A;Adamson A;Hastings MH
哺乳动物的昼夜节律由下丘脑视交叉上核（SCN）控制，其中20,000个时钟细胞连接在一起形成一个强大的计时网络。在缺乏网络级细胞相互作用的情况下，SCN作为时钟失效。然而，指导网络功能的不同细胞群（节点）的拓扑结构和特定角色尚不清楚。为了表征其组成细胞和网络结构，我们对SCN器官型切片进行了单细胞测序，并在昼夜节律中鉴定了11个不同的神经元亚群。我们定义了这些节点之间的神经肽能信号轴，并建立了神经肽特异性网络拓扑结构。这揭示了它们的时间可塑性，在昼夜节律中被上调。通过交叉遗传学和实时成像，我们研究了Prok2 - ProkR2神经肽能轴对整个网络时间保持的贡献。我们发现Prok2 - ProkR2信号作为SCN周期和节律性的关键调节因子，并有助于定义支撑强大的昼夜节律协调的网络水平特性。这些结果突出了神经肽调节的跨SCN时间信息交流的多样性和独特贡献。11个不同的神经元亚群构成了哺乳动物下丘脑的中央生物钟，并通过神经肽调节通讯的不同和独特贡献来整合时间信息。
Circadian rhythms in mammals are governed by the hypothalamic suprachiasmatic nucleus (SCN), in which 20,000 clock cells are connected together into a powerful time‐keeping network. In the absence of network‐level cellular interactions, the SCN fails as a clock. The topology and specific roles of its distinct cell populations (nodes) that direct network functions are, however, not understood. To characterise its component cells and network structure, we conducted single‐cell sequencing of SCN organotypic slices and identified eleven distinct neuronal sub‐populations across circadian day and night. We defined neuropeptidergic signalling axes between these nodes, and built neuropeptide‐specific network topologies. This revealed their temporal plasticity, being up‐regulated in circadian day. Through intersectional genetics and real‐time imaging, we interrogated the contribution of the Prok2‐ProkR2 neuropeptidergic axis to network‐wide time‐keeping. We showed that Prok2‐ProkR2 signalling acts as a key regulator of SCN period and rhythmicity and contributes to defining the network‐level properties that underpin robust circadian co‐ordination. These results highlight the diverse and distinct contributions of neuropeptide‐modulated communication of temporal information across the SCN. Eleven distinct neuronal sub‐populations constitute the central circadian clock in the mammalian hypothalamus, and integrate temporal information via diverse and distinct contributions of neuropeptide‐modulated communication.
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影响因子：
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作者：
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Okamura, Hitoshi
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连接SCN中的神经活动和分子振荡。
影响因子：
34.7
作者：
Colwell, Christopher S.
通讯作者：
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