Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq

• Published in: Cell reports (Cambridge) Vol. 16; no. 4; pp. 1126 - 1137
• Main Authors: Gokce, Ozgun, Stanley, Geoffrey M., Treutlein, Barbara, Neff, Norma F., Camp, J. Gray, Malenka, Robert C., Rothwell, Patrick E., Fuccillo, Marc V., Südhof, Thomas C., Quake, Stephen R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.07.2016; Elsevier
• Subjects: Animals; Astrocytes - metabolism; Astrocytes - physiology; Behavior, Addictive - metabolism; Behavior, Addictive - physiopathology; Cell Differentiation - physiology; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - physiopathology; Corpus Striatum - metabolism; Corpus Striatum - physiology; Ependyma - metabolism; Ependyma - physiology; Male; Mice; Neurons - metabolism; Neurons - physiology; Oligodendroglia - metabolism; Oligodendroglia - physiology; RNA - genetics; Transcription Factors - metabolism; Transcriptome - physiology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.06.059

The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed ten differentiated, distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSNs) that have specific markers and that overexpress genes linked to cognitive disorders and addiction. We also describe continuous cellular identities, which increase heterogeneity within discrete cell types. Finally, we identified cell type-specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns. Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states. [Display omitted] •Transcriptomes of 1,208 single striatal cells•Description of previously unknown medium spiny neuron subtypes•Discrete cell types that exist in a continuous spectrum of transcriptional states•Neurons that have the largest transcriptome and more complex splicing patterns The striatum, the gateway to basal ganglia circuitry, is critical for motor functions. However, its cell types are incompletely characterized. Gokce et al. reveal the diversity of striatal cells using scRNA-seq. They also describe continuous expression gradients within all MSN subtypes and astrocytes that may be fundamental to transcriptional diversity.