Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain

Arpiar Saunders; Evan Z Macosko; Alec Wysoker; Melissa Goldman; Fenna M Krienen; Heather de Rivera; Elizabeth Bien; Matthew Baum; Laura Bortolin; Shuyu Wang; Aleksandrina Goeva; James Nemesh; Nolan Kamitaki; Sara Brumbaugh; David Kulp; Steven A McCarroll

doi:10.1016/j.cell.2018.07.028

Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain

Cell. 2018 Aug 9;174(4):1015-1030.e16. doi: 10.1016/j.cell.2018.07.028.

Authors

Affiliations

¹ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: asaunders@genetics.med.harvard.edu.
² Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: emacosko@broadinstitute.org.
³ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁴ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁵ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: mccarroll@genetics.med.harvard.edu.

Abstract

The mammalian brain is composed of diverse, specialized cell populations. To systematically ascertain and learn from these cellular specializations, we used Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9 regions of the adult mouse brain. We identified 565 transcriptionally distinct groups of cells using computational approaches developed to distinguish biological from technical signals. Cross-region analysis of these 565 cell populations revealed features of brain organization, including a gene-expression module for synthesizing axonal and presynaptic components, patterns in the co-deployment of voltage-gated ion channels, functional distinctions among the cells of the vasculature and specialization of glutamatergic neurons across cortical regions. Systematic neuronal classifications for two complex basal ganglia nuclei and the striatum revealed a rare population of spiny projection neurons. This adult mouse brain cell atlas, accessible through interactive online software (DropViz), serves as a reference for development, disease, and evolution.

Keywords: basal ganglia; brain; single-cell; striatum; transcriptional programs.

Publication types

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

MeSH terms

Animals
Brain / growth & development
Brain / metabolism*
Cell Lineage*
Gene Expression Profiling
Gene Expression Regulation, Developmental*
Gene Regulatory Networks*
High-Throughput Nucleotide Sequencing
Male
Mice
Mice, Inbred C57BL
Single-Cell Analysis / methods*
Transcriptome*

Abstract

Publication types

MeSH terms

Grants and funding