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

Shristi Pandey; Karthik Shekhar; Aviv Regev; Alexander F Schier

doi:10.1016/j.cub.2018.02.040

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

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

Authors

Shristi Pandey¹, Karthik Shekhar², Aviv Regev³, Alexander F Schier⁴

Affiliations

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.

Publication types

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

MeSH terms

Animals
Gene Expression Regulation, Developmental*
Habenula / anatomy & histology*
Habenula / growth & development
Habenula / metabolism
High-Throughput Nucleotide Sequencing / methods*
Larva
Neurogenesis
Neurons / cytology*
Neurons / metabolism
Single-Cell Analysis / methods*
Zebrafish / genetics*
Zebrafish / growth & development
Zebrafish / physiology
Zebrafish Proteins / genetics*

Substances

Zebrafish Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding