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Curr Biol. 2018 Apr 2;28(7):1052-1065.e7. doi: 10.1016/j.cub.2018.02.040. Epub 2018 Mar 22.

Comprehensive Identification and Spatial Mapping of Habenular Neuronal Types Using Single-Cell RNA-Seq.

Author information

1
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: p.shristi@gmail.com.
2
Klarman Cell Observatory, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
3
Klarman Cell Observatory, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA; Howard Hughes Medical Institute and Koch Institute of Integrative Cancer Research Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA.
4
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA; Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA; Biozentrum, University of Basel, Basel, Switzerland; Allen Discovery Center for Cell Lineage Tracing, University of Washington, Seattle, WA 98195, USA. Electronic address: schier@fas.harvard.edu.

Abstract

The identification of cell types and marker genes is critical for dissecting neural development and function, but the size and complexity of the brain has hindered the comprehensive discovery of cell types. We combined single-cell RNA-seq (scRNA-seq) with anatomical brain registration to create a comprehensive map of the zebrafish habenula, a conserved forebrain hub involved in pain processing and learning. Single-cell transcriptomes of ∼13,000 habenular cells with 4× cellular coverage identified 18 neuronal types and dozens of marker genes. Registration of marker genes onto a reference atlas created a resource for anatomical and functional studies and enabled the mapping of active neurons onto neuronal types following aversive stimuli. Strikingly, despite brain growth and functional maturation, cell types were retained between the larval and adult habenula. This study provides a gene expression atlas to dissect habenular development and function and offers a general framework for the comprehensive characterization of other brain regions.

KEYWORDS:

adult; habenula; in situ atlas; larva; neuronal types; single-cell RNA-seq; transcriptomes; zebrafish

PMID:
29576475
PMCID:
PMC6042852
[Available on 2019-04-02]
DOI:
10.1016/j.cub.2018.02.040

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