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

Accepted version
Peer-reviewed

Change log

Authors

Dowsett, Georgina KC  ORCID logo  https://orcid.org/0000-0002-2134-8554
Bauder, Corinna A 

Abstract

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.

Description

The hypothalamus plays a key role in coordinating fundamental body functions. Despite recent progress in single-cell technologies, a unified catalogue 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 SmartSeq2 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, it can serve as an important platform to unravel the functional organization of hypothalamic neurocircuits, and to identify druggable targets for treating metabolic disorders.

Keywords

food intake, Hypothalamus, metabolism

Journal Title

Nat Metab

Conference Name

Journal ISSN

2522-5812
2522-5812

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
Society for Endocrinology (unknown)
Wellcome Trust (208363/Z/17/Z)
Biotechnology and Biological Sciences Research Council (BB/S017593/1)
MRC (MC_UU_00014/1)
MRC (MC_UU_00014/5)
UKRI(MRC and BBSRC), Wellcome
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