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

Science. 2018 Nov 16;362(6416):eaau5324. doi: 10.1126/science.aau5324. Epub 2018 Nov 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atlases as Topic*
  • Female
  • Galanin / genetics
  • Gene Expression Profiling*
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Neurons / metabolism
  • Neurons / physiology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide / genetics
  • Preoptic Area / cytology
  • Preoptic Area / metabolism
  • Preoptic Area / physiology*
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Social Behavior


  • Adcyap1 protein, mouse
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Galanin

Associated data

  • Dryad/10.5061/dryad.8t8s248