HypoMap—a unified single-cell gene expression atlas of the murine hypothalamus

• Published in: Nature metabolism Vol. 4; no. 10; pp. 1402 - 1419
• Main Authors: Steuernagel, Lukas, Lam, Brian Y. H., Klemm, Paul, Dowsett, Georgina K. C., Bauder, Corinna A., Tadross, John A., Hitschfeld, Tamara Sotelo, del Rio Martin, Almudena, Chen, Weiyi, de Solis, Alain J., Fenselau, Henning, Davidsen, Peter, Cimino, Irene, Kohnke, Sara N., Rimmington, Debra, Coll, Anthony P., Beyer, Andreas, Yeo, Giles S. H., Brüning, Jens C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2022
• Subjects: 38/32; 38/39; 45/91; 631/114; 631/378/1488/1562; 631/443/319/367/1562; 64/60; Animals; Biomedical and Life Sciences; Gene Expression; Glucagon-Like Peptide-1 Receptor - genetics; Hypothalamus - metabolism; Life Sciences; Mice; Neurons - metabolism; Sequence Analysis, RNA
• ISSN: 2522-5812
• DOI: 10.1038/s42255-022-00657-y

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. Steuernagel and Lam et al. present HypoMap, an integrated reference atlas of the murine hypothalamus based on 384,925 hypothalamic cells from publicly available single-cell sequencing datasets.