title: Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons.
abstract: In brain, signaling mediated by cell adhesion molecules defines the identity and functional properties of synapses. The specificity of presynaptic and postsynaptic interactions that is presumably mediated by cell adhesion molecules suggests that there exists a logic that could explain neuronal connectivity at the molecular level. Despite its importance, however, the nature of such logic is poorly understood, and even basic parameters, such as the number, identity, and single-cell expression profiles of candidate synaptic cell adhesion molecules, are not known. Here, we devised a comprehensive list of genes involved in cell adhesion, and used single-cell RNA sequencing (RNAseq) to analyze their expression in electrophysiologically defined interneurons and projection neurons. We compared the cell type-specific expression of these genes with that of genes involved in transmembrane ion conductances (i.e., channels), exocytosis, and rho/rac signaling, which regulates the actin cytoskeleton. Using these data, we identified two independent, developmentally regulated networks of interacting genes encoding molecules involved in cell adhesion, exocytosis, and signal transduction. Our approach provides a framework for a presumed cell adhesion and signaling code in neurons, enables correlating electrophysiological with molecular properties of neurons, and suggests avenues toward understanding synaptic specificity.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; Brain Research Institute, University of Zürich, 8057 Zurich, Switzerland; foldy@hifo.uzh.ch tcs1@stanford.edu.
authors.forename: Csaba
authors.initials: C
authors.lastname: Földy
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305;
authors.forename: Spyros
authors.initials: S
authors.lastname: Darmanis
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045;
authors.forename: Jason
authors.initials: J
authors.lastname: Aoto
authors.affiliation: Nancy Pritzker Laboratory, Stanford University, Stanford, CA 94305;
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305 foldy@hifo.uzh.ch tcs1@stanford.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000235:genetics; D005089:Exocytosis / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D017423:Sequence Analysis, RNA / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics; D059010:Single-Cell Analysis / Q000379:methods*; D013569:Synapses / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules
keywords: RNAseq; cell adhesion; single cell; synapse