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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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“SCN neurons were identified among subpopulations of hypothalamic GABAergic neurons based on the expression of known SCN-enriched transcripts( 15, 20, 21 ) such as Avp , Vip , Nms , and Lhx1 (see Materials Methods; Fig.”
InfluentialSelf-citationKim, B., Kim, J., Chun, M., Park, I., Choi, M., Kim, K., & Choe, H. K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.02.184119
The cell-autonomous clock of VIP receptor VPAC2 cells drives circadian behaviourPreprint
Hamnett, R., Chesham, J. E., Maywood, E. S., & Hastings, M. H. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.02.232462
“…p = 0.004 (vs. Bmal1 Flx/- ), p = 0.002 (vs. VPAC2Cre/ Bmal1 WT/- )), consistent with some cells co-expressing AVP and VPAC2 (Patton et al., 2020; Wen et al., 2020), and the Avp gene being a circadian clock-controlled target of the BMAL1-dependent TTFL (Jin et al., 1999; Mieda et al., 2015).”
InfluentialStudying the regulation and development of circadian clock by systems biology approaches
Wang, H. (2020) · doi:10.53846/goediss-8221
Self-citationAltered circadian rhythms and sleep in a new Angelman Syndrome mouse modelPreprint
Shi, S.-Q., Mahoney, C. E., Houdek, P., Zhao, W., Anderson, M. P., Zhuo, X., Beaudet, A. L., Sumová, A., Scammell, T. E., & Johnson, C. H. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.26.465956
Development of a bubble-based single cell picking system
Wang, R., Liu, B., Gong, J., Zhang, J., Gao, M., Zhang, L., Wang, X., Chen, S., Hong, J., & Gui, L. (2022) · Journal of Micromechanics and Microengineering · doi:10.1088/1361-6439/ac4c96
A subtype of melanopsin ganglion cells encodes ground luminancePreprint
Berry, M. H., Moldavan, M., Garrett, T. R., Meadows, M. A., Cravetchi, O., White, E., von Gersdorff, H., Wright, K. M., Allen, C. N., & Sivyer, B. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.06.485949
Single-cell Analysis of Mammalian Circadian Pacemaker
(2020) · 中国科学院院刊：英文版 · doi:10.3724/sp.j.7101866541
Gradinaru, V., Kahan, A., Coughlin, G. M., Borsos, M., & Brunton, B. W. (2022) · Research Square · doi:10.21203/rs.3.rs-2069847/v1
Bafna, A., Banks, G. T., Hastings, M. H., & Nolan, P. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.15.515402
Moysés‐Oliveira, M., Favilla, B. P., Melaragno, M. I., & Tufik, S. B. (2023) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2023.06.014
Narain, P., Petković, A., Šušić, M., Haniffa, S., Drou, N., Arnoux, M., Anwar, M., & Chaudhury, D. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.05.556324
“S2) (69,70).”
Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes
Ryu, J. E., Shim, K.-W., Roh, H. W., Park, M., Lee, J., & Kim, E. Y. (2024) · eLife · doi:10.7554/elife.96357.3
Honma, S. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/bk9781839167553-00107
Gene expression plasticity of the mammalian brain circadian clock in response to photoperiodPreprint
Cox, O., Giannoni‐Guzmán, M. A., Cartailler, J., Cottam, M. A., & McMahon, D. G. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.16.580759
“To focus on genes robustly expressed in the SCN in our dataset, we used gene expression data from recent scRNA studies of SCN neurons for exploratory analysis (Morris et al., 2021; Wen et al., 2020).”
MethodAstrocytes in the mouse suprachiasmatic nuclei respond directly to glucocorticoids feedbackPreprint
Händler, K., Sreenivasan, V. K. A., Pilorz, V., Olano-Bringas, J., Escobar, L., Bengoa‐Vergniory, N., Oster, H., Spielmann, M., & Astiz, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.04.583323
“Moreover, the total number of cells per cluster that we have identified at PND30 fits with the expected proportion of different cell types in the SCN (i.e.: neuron:astrocyte ratio of 3:1, around 5% of NG2 cells/oligodendrocytes and below 2-3% of endothelial cells and microglia 59 ).”
BackgroundMethodNovel clock neuron subtypes regulate temporal aspects of sleepPreprint
Ma, D., Le, J. Q., Dai, X., Díaz, M. M., Abruzzi, K. C., & Rosbash, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.03.592478
Self-citationNeurodegenerative diseases and circadian rhythm dysfunction: A bidirectional nexus
Samanta, S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95735-9.00033-4
eLife Assessment: OpenNucleome for high resolution nuclear structural and dynamical modeling
Collepardo, R. (2024) · eLife · doi:10.7554/elife.93223.2.sa3
OpenNucleome for high resolution nuclear structural and dynamical modelingPreprint
Lao, Z., Kamat, K., Jiang, Z., & Zhang, B. (2024) · eLife · doi:10.7554/elife.93223.2 · Cited by 1
Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytesPreprint
Ryu, J. E., Shim, K.-W., Roh, H. W., Park, M., Lee, J., & Kim, E. Y. (2024) · eLife · doi:10.7554/elife.96357.2
Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer micePreprint
Chen, J., Richardson, P. R., Kirby, C., Eddy, S. R., & Hoekstra, H. E. (2024) · eLife · doi:10.7554/elife.103109.1
The Functional Connectome Mediating Circadian Synchrony in the Suprachiasmatic NucleusPreprint
Nikhil, K. L., Singhal, B., Granados‐Fuentes, D., Li, J.-S., Kiss, I. Z., & Herzog, E. D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.06.627294
Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer micePreprint
Chen, J., Richardson, P. R., Kirby, C., Eddy, S. R., & Hoekstra, H. E. (2025) · eLife · doi:10.7554/elife.103109.2
Bafna, A., Banks, G. T., Vasilyev, V., Dallmann, R., Hastings, M. H., & Nolan, P. M. (2025) · eLife · doi:10.7554/elife.102019.2
Magaña, I., Taufique, S. K. T., Shan, Y., Shen, M., Ehichioya, D. E., Takahashi, J. S., Yamazaki, S., & Obata, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.16.688705
Maloney, G. E., Cloutier, M., Provost, M. J., Srivastava, L. K., & Cermakian, N. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.12.029
Harding, C., Bechtold, D. A., & Brown, T. M. (2020) · Figshare · doi:10.6084/m9.figshare.13031465
Harding, C., Bechtold, D. A., & Brown, T. M. (2020) · Figshare · doi:10.6084/m9.figshare.13031468
Harding, C., Bechtold, D. A., & Brown, T. M. (2020) · Figshare · doi:10.6084/m9.figshare.13031453
Harding, C., Bechtold, D. A., & Brown, T. M. (2020) · Figshare · doi:10.6084/m9.figshare.13031459
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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