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Spatiotemporal single-cell analysis of gene expression in the mouse suprachiasmatic nucleus
Abstract
Mammalian circadian behaviors are orchestrated by the suprachiasmatic nucleus (SCN) in the ventral hypothalamus, but the number of SCN cell types and their functional roles remain unclear. We have used single-cell RNA-sequencing to identify the basic cell types in the mouse SCN and to characterize their circadian and light-induced gene expression patterns. We identified eight major cell types, with each type displaying a specific pattern of circadian gene expression. Five SCN neuronal subtypes, each with specific combinations of markers, differ in their spatial distribution, circadian rhythmicity and light responsiveness. Through a complete three-dimensional reconstruction of the mouse SCN at single-cell resolution, we obtained a standardized SCN atlas containing the spatial distribution of these subtypes and gene expression. Furthermore, we observed heterogeneous circadian gene expression between SCN neuron subtypes. Such a spatiotemporal pattern of gene regulation within the SCN may have an important function in the circadian pacemaker.
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“suggesting that the pacemaker cells are at a different phase of the circadian cycle of gene expression from the rest of the brain, consistent with previous findings117”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [117]
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Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108
Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N. J., Livak, K. J., Mikkelsen, T. S., & Rinn, J. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2859 · Cited by 7,314
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055
Scenic: single-cell regulatory network inference and clustering.
Aibar, S., González-Blas, C. B., Moerman, T., Huynh-Thu, V. A., Imrichova, H., Hulselmans, G., Rambow, F., Marine, J.-C., Geurts, P., Aerts, J., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4463 · Cited by 6,520
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Wolff, C. A., Gutierrez‐Monreal, M. A., Meng, L., Zhang, X., Douma, L. G., Costello, H. M., Douglas, C. M., Ebrahimi, E., Pham, A. T., Oliveira, A. C. D. S., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2022.111982 · Cited by 158
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Todd, W. D., Venner, A., Anaclet, C., Broadhurst, R. Y., Luca, R. D., Bandaru, S. S., Issokson, L., Hablitz, L. M., Cravetchi, O., Arrigoni, E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17197-2 · Cited by 145
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“Since one limitation of scRNA-seq is that all expressed genes are not detected in each library, we characterized each neuron by matching transcriptomes against the recently published scRNA-seq atlas of SCN neurons (Wen et al., 2020) to classify their type (prediction scores are shown in Table S1; see STAR Methods).”
BackgroundMethodSelf-citationCoupled network of the circadian clocks: a driving force of rhythmic physiology
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BackgroundXu, P., Berto, S., Kulkarni, A., Jeong, B., Joseph, C., Cox, K. H., Greenberg, M. E., Kim, T.-K., Konopka, G., & Takahashi, J. S. (2021) · Neuron · doi:10.1016/j.neuron.2021.07.026 · Cited by 90
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Colwell, C. S. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148288 · Cited by 90
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BackgroundMicrofluidics for Neuronal Cell and Circuit Engineering
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Morris, E. L., Patton, A. P., Chesham, J. E., Crisp, A., Adamson, A. D., & Hastings, M. H. (2021) · The EMBO Journal · doi:10.15252/embj.2021108614 · Cited by 87
“Nevertheless, five SCN subtypes were identified with cluster-specific marker genes, including Avp , Grp , Vip , Cck and C1ql3 and SCN-enriched genes Prok2 , Rasl11b , Nr1d1 , Rgs16 and Rasd1 exhibited strong circadian expression in serial tissue samples.”
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“Indeed, a recent study suggested that GABA signaling arising from the SCN may play a regulatory role in preventing RP3VKISS neuron activation at non-surge times (Jamieson et al., 2021); however, such GABA effects were proposed to be indirect on RP3VKISS neurons and mediated via a multi-synaptic pathway that involves o…”
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Self-citationPatton, A. P., Edwards, M. D., Smyllie, N. J., Hamnett, R., Chesham, J. E., Brancaccio, M., Maywood, E. S., & Hastings, M. H. (2020) · Nature Communications · doi:10.1038/s41467-020-17110-x · Cited by 74
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BackgroundKim, D. W., Liu, K., Wang, Z. Q., Zhang, Y. S., Bathini, A., Brown, M. P., Lin, S. H., Washington, P. W., Sun, C., Lindtner, S., et al. (2021) · Communications Biology · doi:10.1038/s42003-020-01616-7 · Cited by 54
Self-citationGABAergic mechanisms in the suprachiasmatic nucleus that influence circadian rhythm
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Self-citationHerb, B. R., Glover, H. J., Bhaduri, A., Colantuoni, C., Bale, T. L., Siletti, K., Linnarsson, S., Hodge, R. D., Lein, E. S., Kriegstein, A. R., et al. (2023) · Science Advances · doi:10.1126/sciadv.adf6251 · Cited by 57
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“AVP-positive neurons and VIP-positive neurons (6, 32).”
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BackgroundTargeting NR1D1 in organ injury: challenges and prospects
Zhangsun, Z., Xu, X., Escames, G., Lei, W., Zhao, L., Zhou, Y., Tian, Y., Ren, Y., Acuña-Castroviejo, D., & Yang, Y. (2023) · Military Medical Research · doi:10.1186/s40779-023-00495-3 · Cited by 29
“On the other hand, it maintains the synchronized rhythms of behavior and physiology in cells and tissues by aligning circadian gene oscillations within extra-SCN neurons and peripheral tissues [19, 22, 23].”
BackgroundLeptin receptor neurons in the dorsomedial hypothalamus input to the circadian feeding network
Tang, Q., Godschall, E., Brennan, C. D., Zhang, Q., Abraham‐Fan, R., Williams, S. P., Güngül, T. B., Onoharigho, R., Buyukaksakal, A., Salinas, R., et al. (2023) · Science Advances · doi:10.1126/sciadv.adh9570 · Cited by 33
“Although it is not required for the expression of food ( 35 , 36 ) and validated on the basis of Allen Brain Atlas Mouse Brain in situ hybridization data ( 57 ).”
Auerbach, B. J., FitzGerald, G. A., & Li, M. (2022) · Nature Communications · doi:10.1038/s41467-022-34185-w · Cited by 29
“Further details of this procedure can be viewed in Supplementary Methods 6 and 7.”
BDE-47 Causes Depression-like Effects in Zebrafish Larvae via a Non-Image-Forming Visual Mechanism
Cao, M., Xu, T., Zhang, H., Wei, S., Wang, H., Song, Y., Guo, X., Chen, D., & Yin, D. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.3c01716 · Cited by 27
Self-citationHuang, Y., Wang, A., Zhou, W., Li, B., Zhang, L., Rudolf, A. M., Jin, Z., Hambly, C., Wang, G., & Speakman, J. R. (2024) · Nature Communications · doi:10.1038/s41467-024-46589-x · Cited by 24
Energy balance drives diurnal and nocturnal brain transcriptome rhythms
van Rosmalen, L., Deota, S., Maier, G., Le, H. D., Lin, T. C., Ramasamy, R. K., Hut, R. A., & Panda, S. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113951 · Cited by 23
Jha, P. K., Bouâouda, H., Kalsbeek, A., & Challet, É. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.12.011 · Cited by 23
Yamaguchi, Y., Murai, I., Goto, K., Doi, S., Zhou, H., Setsu, G., Shimatani, H., Okamura, H., Miyake, T., & Doi, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-01764-8 · Cited by 21
Xiong, X., Hu, T., Yin, Z., Zhang, Y., Chen, F., & Lei, P. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.944283 · Cited by 26
“Currently, the mechanism by which bright light therapy (BLT) treats sleep disorders in patients with AD is believed to be through retinal neurons; these retinal neurons contain a photosensitive pigment that can transmit light signals to the suprachiasmatic nucleus (SCN), which is the epicenter of circadian rhythms and…”
BackgroundReduced VIP Expression Affects Circadian Clock Function in VIP-IRES-CRE Mice (JAX 010908)
Joye, D. A. M., Rohr, K. E., Keller, D., Inda, T., Telega, A., Pancholi, H., Carmona‐Alcocer, V., & Evans, J. A. (2020) · Journal of Biological Rhythms · doi:10.1177/0748730420925573 · Cited by 23
“It is well appreciated that VIP is an important neuropeptide that regulates circadian function, but the SCN contains many other cell types whose roles are not well understood (Wen et al., 2020).”
BackgroundQin, Y., Liu, Z., Gao, S., Martínez-Vasallo, C., Long, Y., Zhu, X., Liu, B., Gao, Y., Xu, X., Nohales, M. A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59424-8 · Cited by 27
“We also utilized the z-score to compute the statistical signi fi cance of phase and amplitude as described by Wen et al. 30 .”
InfluentialDrunen, R. V., Dai, Y., Wei, H., Fekry, B., Noori, S., Shivshankar, S., Bravo, R., Zhao, Z., Yoo, S. H., Justice, N. J., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114380 · Cited by 24
“Cluster identities were largely consistent with published single-cell datasets of the SCN 45 and the whole and lateral hypothalamus.”
BackgroundResultAstrocyte Clocks and Glucose Homeostasis
Barca‐Mayo, O., & López, M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.662017 · Cited by 23
“Briefly, the SCN is a heterogeneous and complex bilateral nucleus (8, 9) comprising approximately 10,000 self-oscillating neurons on each side, in mice (10–12).”
BackgroundHu, S., Luo, L., & Zeng, L. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2040945 · Cited by 21
Bartholomai, B. M., Gladfelter, A. S., Loros, J., & Dunlap, J. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2203078119 · Cited by 21
Koo, K., Kim, C., Kim, H., Cho, Y., Suhito, I. R., & Kim, T. P. (2023) · Advanced Science · doi:10.1002/advs.202207084 · Cited by 21
Tsuno, Y., Peng, Y., Horike, S., Wang, M., Matsui, A., Yamagata, K., Sugiyama, M., Nakamura, T. J., Daikoku, T., Maejima, T., et al. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002281 · Cited by 21
Circadian Regulation of Apolipoproteins in the Brain: Implications in Lipid Metabolism and Disease
Lee, C., Murrell, C. E., Chu, A., & Pan, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417415 · Cited by 20
“Wen et al. have identified eight primary cell types, each with a specific mode of circadian gene expression, according to single-cell RNA-sequencing [56].”
BackgroundA whole-brain single-cell atlas of circadian neural activity in mice
Yamashita, K., Kinoshita, F. L., Yoshida, S., Matsumoto, K., Mitani, T. T., Fujishima, H., Minami, Y., Morii, E., Yamada, R. G., Okada, S., et al. (2025) · Science · doi:10.1126/science.aea3381 · Cited by 24
Swift, J., Greenham, K., Ecker, J. R., Coruzzi, G. M., & McClung, C. R. (2021) · The Plant Journal · doi:10.1111/tpj.15589 · Cited by 22
High-Fat Nutritional Challenge Reshapes Circadian Signatures in Murine Extraorbital Lacrimal Glands
Zou, S., Jiao, X., Liu, J., Qi, D., Pei, X., Lu, D., Huang, S., & Li, Z. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.5.23 · Cited by 21
“114,115 In conclusion, our study reveals that the nutritional challenge from an HFD modulates an unexpected plasticity of the lacrimal glands in terms of its circadian transcriptomic profile and diurnal changes in cell size, immune cell recruitment, and secretion response.”
Impact of circadian clock dysfunction on human health
Samanta, S., & Ali, S. A. (2022) · Exploration of neuroscience · doi:10.37349/en.2022.00002 · Cited by 21
“The circadian clock regulates the rhythmic expression of numerous genes and is also involved in protein processing and transmission of protein aggregates [68, 72, 73].”
BackgroundHiggs, M. J., Hill, M., John, R. M., & Isles, A. R. (2022) · BMC Genomics · doi:10.1186/s12864-022-08986-8 · Cited by 20
“242 Suprachiasmatic Nucleus (SCN) (5) 243 Analysis of the 10x chromium data of SCN neurons (Supplemental Table S13) revealed a significant 244 over-representation (q = 1.”
BackgroundInfluentialThe genomic basis of temporal niche evolution in a diurnal rodent
Richardson, R., Feigin, C. Y., Baño‐Otálora, B., Johnson, M. R., Allen, A. E., Park, J., McDowell, R. J., Mereby, S. A., Lin, I., Lucas, R. J., et al. (2023) · Current Biology · doi:10.1016/j.cub.2023.06.068 · Cited by 20
Son, G., Neylan, T. C., & Grinberg, L. T. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00695-4 · Cited by 21
“Astrocytes in culture exhibit daily rhythms [76], cytokine expression oscillates in astrocytes [77], and core clock genes such as Dbp , Nr1d1, and Fabp7 show higher amplitude in mouse astrocytes than in neurons [64].”
BackgroundChronic sleep deprivation impairs retinal circadian transcriptome and visual function
Huang, S., Zhang, W., Xuan, S., Si, H., Huang, D., Ba, M., Qi, D., Pei, X., Lu, D., & Li, Z. (2024) · Experimental Eye Research · doi:10.1016/j.exer.2024.109907 · Cited by 21
Duan, J., Ngo, M. N., Karri, S. S., Tsoi, L. C., Gudjonsson, J. E., Shahbaba, B., Lowengrub, J. S., & D, B. A. M. (2024) · Nature Communications · doi:10.1038/s41467-024-48041-6 · Cited by 20
“For training, we chose GSE157077 36 , a time series of bulk RNAseq data collected from the mouse SCN every four hours under a regular 12:12 light-dark cycle starting at ZT0.”
InfluentialDaily rhythms in gene expression of the human parasite Schistosoma mansoni
Rawlinson, K. A., Reid, A. J., Lu, Z., Driguez, P., Wawer, A., Coghlan, A., Sankaranarayanan, G., Buddenborg, S. K., Soria, C. D., McCarthy, C. A., et al. (2021) · BMC Biology · doi:10.1186/s12915-021-01189-9 · Cited by 21
Karin, J., Bornfeld, Y., & Nitzan, M. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01663-5 · Cited by 19
Zong, W., Seney, M. L., Ketchesin, K. D., Gorczyca, M. T., Liu, A. C., Esser, K. A., Tseng, G. C., McClung, C. A., & Huo, Z. (2023) · Statistics in Medicine · doi:10.1002/sim.9803 · Cited by 20
“For active sampling design, 6 time points (every 4 hours) per cycle across one or multiple full cycles have been widely adopted in many studies (26, 27, 38).”
MethodChen, R., Routh, B. N., Gaudet, A. D., & Fonken, L. K. (2023) · Journal of Biological Rhythms · doi:10.1177/07487304231178950 · Cited by 21
“, 2014), which continues in adulthood (Wen et al., 2020).”
Circadian medicine for aging attenuation and sleep disorders: Prospects and challenges
Banerjee, S., & Ray, S. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102387 · Cited by 18
Evans, J. A., & Schwartz, W. J. (2023) · Journal of Comparative Physiology A · doi:10.1007/s00359-023-01659-1 · Cited by 18
“Like many fields, circadian biology is incorporating new techniques to identify and characterize cellular diversity in form and function (e.g., Shan et al. 2020; Wen et al. 2020; Todd et al. 2020; McManus et al. 2022).”
Hamnett, R., Chesham, J. E., Maywood, E. S., & Hastings, M. H. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2015-20.2020 · Cited by 18
“, 2020); and, given both their shell localization and likely expression of glutamate receptor NR2C (Wen et al., 2020), they may also act as a conduit for astrocytically derived period cues (Brancaccio et al.”
BackgroundInfluential
Metadata
- Authors
- Wen, S., Ma, D., Zhao, M., Xie, L., Wu, Q., Gou, L., Zhu, C., Fan, Y., Wang, H., & Yan, J.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Yan, Jun
- Venue
- Nature Neuroscience
- Published
- 2020-02-17
- Volume
- 23
- Issue
- 3
- Pages
- 456-467
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W3005834749
- Cited by
- 328
- References
- 58
- Citations by year
- 2026: 35 · 2025: 50 · 2024: 75 · 2023: 54 · 2022: 37 · 2021: 45 · 2020: 32
- FWCI
- 21.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Shanghai (16ZR1448800)
- National Natural Science Foundation of China (31571209)
- Science and Technology Commission of Shanghai Municipality (No. 2018SHZDZX05)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Keywords
- suprachiasmatic nucleus, circadian rhythm, circadian pacemaker, neuronal cell types, circadian gene expression, light-induced gene expression, single-cell RNA sequencing, 3D reconstruction, mice, ventral hypothalamus
- MeSH terms
- Animals, Atlases as Topic, Circadian Rhythm, Gene Expression Regulation, Light, Male, Mice, Inbred C57BL, Neurons, Photic Stimulation, Suprachiasmatic Nucleus, Gene Expression, Genomics, Mice, Circadian Rhythm Signaling Peptides and Proteins, Single-Cell Analysis
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