GSE208355
HypoMap – a unified single cell gene expression atlas of the murine hypothalamus
The hypothalamus plays a key role in coordinating a plethora of fundamental body functions, such as energy homeostasis, social behavior and sleep. Despite recent progress in single-cell technologies, we still lack a unified catalogue and molecular characterization of the heterogeneous cell types and, specifically, neuronal subtypes in this brain region. Here, we combined 17 publicly available hypothalamic single cell sequencing datasets and in-house single-nuclear sequencing of 36,626 cells to create 'HypoMap', an integrated reference atlas of the murine hypothalamus of 384,925 cells. We have leveraged the power of this vast amount of available data by combining them in a single platform, which allows the future incorporation of additional experiments. We validated HypoMap by comparing data collected from SmartSeq2 and bulk RNA sequencing of selected neuronal cell types with different degrees of cellular heterogeneity. Finally, we identified novel classes of glucagon-like peptide-1 receptor (Glp1r)- and Prepronociceptin (Pnoc-) expressing neurons and validated them using single-molecule in situ hybridization. Collectively, HypoMap provides a unified framework for the systematic functional annotation of murine hypothalamic cell types, and will serve as an important platform for future studies to further unravel the functional organization of hypothalamic neurocircuits, as well as identifying novel druggable targets for treating metabolic disorders. Overall design: We generated bacTRAP RNA-seq datasets of specific hypothalamic cell types, which have been shown to be of critical importance in control of energy and glucose homeostasis, but vary in their heterogeneity and anatomical distribution. To this end, we first crossed mice expressing Cre recombinase in either AgRP neurons, POMC neurons, Pnoc-expressing neurons or in Glp1r-expressing neurons with mice allowing for Cre-dependent expression of a fusion protein of the ribosomal protein L10a and GFP.