Progress in the study of circadian rhythm Center

On February 18, the Journal of Nature Neuroscience published a research paper entitled "spatiotemporal single cell analysis of gene expression in mouse suprachiasmatic nucleus" The research was completed by Yan Jun research group, brain science and intelligent technology innovation center of Chinese Academy of Sciences (Neuroscience Research Institute), Shanghai brain science and brain like research center and State Key Laboratory of neuroscience In this study, single cell sequencing technology was used to systematically classify the suprachiasmatic nucleus, the center of circadian rhythm in mice, and new subtypes of neurons were found The differences of gene expression of these subtypes in circadian rhythm and light stimulation were revealed At the same time, the three-dimensional spatial distribution of all subtypes of cells was completely reconstructed at the level of single cell The neural mechanism of circadian rhythm laid an important foundation Circadian rhythms exist widely in organisms and play an important role in regulating many physiological processes such as exercise, sleep, metabolism, etc It is believed that the circadian rhythm in mammals is controlled by the suprachiasmatic nucleus (SCN) located in the brain SCN can receive the external light and dark signals from the retina, generate the circadian rhythm oscillations on its own, and transmit the circadian rhythm signals to the whole body At the molecular level, circadian rhythms are produced by a series of transcription translation feedback loops (ttfl) composed of a series of core rhythms Previous studies have shown that the expression of core rhythm genes in SCN neurons shows synchronous oscillation, and cells in different spatial positions have different oscillation phases It has been pointed out that SCN cells express a variety of neuropeptides and receptors, and the intercellular communication network formed by them is an important basis for the synchronization of SCN cell rhythmic gene expression Previous studies on SCN only focused on the expression of VIP and AVP, but the overall cell typing, spatial distribution of different cell types in SCN, and how these cell types play a role in circadian rhythm are not clear In this study, we used drop-seq, smfish and LCM SEQ to analyze SCN of mice sampled at different time points of day and night We obtained the expression of gene rhythm in different cell types and reconstructed these cell types in SC 3-D spatial position information in n In this study, we first found that all kinds of non neuron cells, including ependymal cells, glial cells, and so on, have extensive rhythmic gene expression, suggesting that all kinds of cells in SCN have cell-specific rhythmic function Interestingly, the phase of core rhythm gene oscillation in all non neuron cells was significantly later than that in neurons In neurons, SCN neurons have significantly higher core gene expression than non SCN neurons The study group further divided the neurons in SCN into five subtypes, named AVP + / NMS +, GRP + / VIP +, VIP + / NMS +, CCK + / c1ql3 + and CCK + / BDNF + respectively according to their expressed genes (Figure a-b) Among them, AVP + / NMS +, VIP + / NMS + and CCK + / c1ql3 + showed strong rhythmic gene expression (Figure C) The phase of rhythmic gene expression in AVP + / NMS + cells on the dorsal side of SCN and VIP + / NMS + cells on the ventral side was higher than that in CK + / c1ql3 + cells on the anterior side of SCN Through the light stimulation experiment, it was found that different subtypes of SCN had obvious differences in light response, among which GRP + / VIP + cells had the strongest response to light, while CK + / c1ql3 + and CK + / BDNF + cells had the weakest response to light This shows that there is a functional distinction between the generation of rhythmic oscillation and light sensitivity in SCN subtypes Finally, the three-dimensional spatial distribution of SCN neuronal subtypes in SCN was reconstructed completely by tissue transparency imaging (Fig d), and the three-dimensional gene expression gradient (Fig E) in SCN was revealed by laser microdissection combined with RNA sequencing technology, which provided further evidence for the division of SCN cell subtypes and spatial anisotropy in function In this study, advanced single cell technology was used to comprehensively classify, reconstruct and analyze SCN in circadian rhythm Center for the first time The information obtained from different cell types of SCN, spatiotemporal gene expression and cell architecture of neuron subtypes provides important clues for the study of neural mechanism of circadian rhythm in mammals This work can be summarized with f-chart, which implies that SCN, as the core pacemaker of biological rhythm, converts light signals into rhythm signals like a prism, and different neurons produce different phase oscillations, reflecting different times on the ancient sundial in China In human society, circadian rhythm disorder can lead to various diseases including sleep disorders Therefore, it is of great significance to understand how circadian rhythm is produced, maintained and played a role in the nervous system