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Single-cell transcriptomics of suprachiasmatic nuclei reveal a Prokineticin-driven circadian network.

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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.



Prokineticin receptor 2, Prokineticin2, neural network, neuropeptides, single-cell transcriptomics, Animals, Circadian Clocks, Circadian Rhythm, Gastrin-Releasing Peptide, Gastrointestinal Hormones, Gene Expression Regulation, Gene Regulatory Networks, Mice, Neurons, Neuropeptides, Receptors, Bombesin, Receptors, G-Protein-Coupled, Receptors, Peptide, Receptors, Vasopressin, Signal Transduction, Single-Cell Analysis, Suprachiasmatic Nucleus, Transcriptome, Vasoactive Intestinal Peptide, Vasopressins

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Springer Science and Business Media LLC
UKRI|Medical Research Council (MRC) (MC_U105170643)
UKRI|Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R016658/1)