Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region

• Published in: Science (American Association for the Advancement of Science) Vol. 362; no. 6416
• Main Authors: Moffitt, Jeffrey R., Bambah-Mukku, Dhananjay, Eichhorn, Stephen W., Vaughn, Eric, Shekhar, Karthik, Perez, Julio D., Rubinstein, Nimrod D., Hao, Junjie, Regev, Aviv, Dulac, Catherine, Zhuang, Xiaowei
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 16.11.2018
• Subjects: Aggression; Animals; Architecture; Atlases as Topic; Behavior; Brain; Brain architecture; Brain mapping; Child Rearing; Circuits; Female; Fluorescence; Fluorescence in situ hybridization; Functional morphology; Galanin - genetics; Gene expression; Gene Expression Profiling; Gene mapping; Gene sequencing; Heterogeneity; Hybridization; Hypothalamus; Identification; Identification methods; Imaging; In Situ Hybridization, Fluorescence; Infants; Male; Males; Mapping; Mice; Multiplexing; Neuroimaging; Neuromodulation; Neurons; Neurons - metabolism; Neurons - physiology; Nuclei (cytology); Parental behavior; Pituitary Adenylate Cyclase-Activating Polypeptide - genetics; Populations; Preoptic area; Preoptic Area - cytology; Preoptic Area - metabolism; Preoptic Area - physiology; Ribonucleic acid; RNA; Sequence Analysis, RNA - methods; Sexual behavior; Signatures; Single-Cell Analysis - methods; Sleep; Social Behavior; Spatial discrimination; Spatial resolution; Thermoregulation; Thirst; Tissues; Transcription
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aau5324

Spatial transcriptomics can link molecularly described cell types to their anatomical positions and functional roles. Moffitt et al. used a combination of single-cell RNA-sequencing and MERFISH (multiplexed error-robust fluorescence in situ hybridization) to map the identity and location of specific cell types within the mouse preoptic hypothalamus and surrounding areas of the brain (see the Perspective by Tasic and Nicovich). They related these cell types to specific behaviors via gene activity. The approach provides an unbiased description of cell types of the preoptic area, which are important for sleep, thermoregulation, thirst, and social behavior. Science , this issue p. eaau5324 ; see also p. 749 A spatially resolved single-cell transcriptomic study of an essential brain region yields a functionally annotated cell atlas. The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei—including the molecular identity, spatial organization, and function of distinct cell types—is poorly understood. Here, we developed an imaging-based in situ cell-type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.