HypoMap—a unified single-cell gene expression atlas of the murine hypothalamus
Open accessAbstract
The hypothalamus plays a key role in coordinating fundamental body functions. Despite recent progress in single-cell technologies, a unified catalog and molecular characterization of the heterogeneous cell types and, specifically, neuronal subtypes in this brain region are still lacking. Here, we present an integrated reference atlas, ‘HypoMap,’ of the murine hypothalamus, consisting of 384,925 cells, with the ability to incorporate new additional experiments. We validate HypoMap by comparing data collected from Smart-Seq+Fluidigm C1 and bulk RNA sequencing of selected neuronal cell types with different degrees of cellular heterogeneity. Finally, via HypoMap, we identify classes of neurons expressing glucagon-like peptide-1 receptor ( Glp1r ) and prepronociceptin ( Pnoc ), and validate them using single-molecule in situ hybridization. Collectively, HypoMap provides a unified framework for the systematic functional annotation of murine hypothalamic cell types, and it can serve as an important platform to unravel the functional organization of hypothalamic neurocircuits and to identify druggable targets for treating metabolic disorders.
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The HY-EA-Glut-GABA neighbourhood (including subclasses 66 and 73-144, total 1,404 clusters) contains a set of closely related neuronal subclasses from the entire hypothalamus, as well as the striatum-like amygdalar nuclei and caudal PAL regions of CNU that are also known as the extended amygdala.
“The HY–EA-Glut–GABA neighbourhood (including subclasses 66 and 73–144, total 1,404 clusters) contains a set of closely related neuronal subclasses from the entire hypothalamus32,33, as well as the striatum-like amygdalar nuclei (sAMY) and caudal PAL regions of CNU that are also known as the extended amygdala”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [33]
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“Consistent with the broad action of the incretins in the brain and the periphery, the receptors for GIP and GLP-1 receptors show widespread distribution that includes also hypothalamic and hindbrain regions implicated in regulation of body weight and food intake [52–55].”
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Fang, G., Li, B., Zhu, L., Chen, L., Xiao, J., & Chen, J. (2025) · Biomolecules · doi:10.3390/biom15081140 · Cited by 9 · see citing works
Neuronal GPR75 deficiency protects against diet-induced obesity in a humanized mouse model
Sun, X.-N., Funcke, J., Joung, C., Li, C., Cobb, A., Onodera, T., Velasco, J., Wang, M.-Y., Antonellis, P. J., Mazzone, C. M., et al. (2026) · Science Advances · doi:10.1126/sciadv.ady7993 · Cited by 9 · see citing works
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- Authors
- Steuernagel, L., Lam, B. Y. H., Klemm, P., Dowsett, G. K. C., Bauder, C. A., Tadross, J. A., Hitschfeld, T. S., del Rio Martin, A., Chen, W., de Solis, A. J., Fenselau, H., Davidsen, P., Cimino, I., Kohnke, S. N., Rimmington, D., Coll, A. P., Beyer, A., Yeo, G. S. H., & Brüning, J. C.
- Affiliations
- Max Planck Institute for Metabolism Research (DE)
- University of Cambridge (GB)
- University of Cologne (DE)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Beyer, Andreas
- Yeo, Giles S. H.
- Brüning, Jens C.
- ORCID
- Venue
- Nature Metabolism
- Published
- 2022-10-20
- Volume
- 4
- Issue
- 10
- Pages
- 1402-1419
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC9584816
- OpenAlex
- W4306888699
- Cited by
- 267
- References
- 66
- Citations by year
- 2026: 61 · 2025: 87 · 2024: 76 · 2023: 39 · 2022: 4
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo
- Apollo (cc-by)
- Funders
- Wellcome Trust (208363/Z/17/Z)
- Cancer Research UK
- National Institute for Health and Care Research (CL-2019-14-504)
- Society for Endocrinology
- European Commission (HORIZON2020)
- Bundesministerium für Bildung und Forschung
- Max-Planck-Gesellschaft
- Novo Nordisk
- Medical Research Council (MC_UU_00014/1, MC_UU_00014/5, CL-2019-14-504)
- Biotechnology and Biological Sciences Research Council (BB/S017593/1)
- H2020 European Research Council (742106)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- hypothalamus, neuronal cell types, GLP-1 receptor, metabolic disorders, mouse brain, druggable targets
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Hypothalamus, Neurons, Gene Expression, Sequence Analysis, RNA, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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