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

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

Moffitt JR1,2,3,4, Bambah-Mukku D1,4,5, Eichhorn SW1,2,3,4, Vaughn E1,4,5, Shekhar K6, Perez JD1,4,5, Rubinstein ND1,4,5, Hao J1,2,3,4, Regev A1,6,7, Dulac C8,4,5, Zhuang X8,2,3,4.

Author information

1
Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
2
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
3
Department of Physics, Harvard University, Cambridge, MA 02138, USA.
4
Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
5
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
6
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
7
Koch Institute of Integrative Cancer Biology, Department of Biology, MIT, Cambridge, MA 02139, USA.
8
Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA. dulac@fas.harvard.edu zhuang@chemistry.harvard.edu.

Abstract

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.

PMID:
30385464
DOI:
10.1126/science.aau5324

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