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

Abstract

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 10 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 (MSN) which have specific markers and which 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.

Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits

“…In addition, Nrxn1 mRNA is abundantly produced in astrocytes (Zhang et al, 2014; Gokce et al, 2016). Several reports suggested neurexin expression outside of neurons and glia using sensitive RT-PCR assays or immunological approaches, but given the absence of non-brain phenotypes in neurexin mutant mice and the lack of reliable antibodies, these observations need to be validated.…”

Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity

“…Recent advances in single-cell RNA sequencing (scRNA-seq) have facilitated the transcriptional cataloguing of cell types in many tissues, including those in the nervous system (Gokce et al, 2016; Macosko et al, 2015; Tasic et al, 2016; Zeisel et al, 2015). While cell diversity in the cerebral cortex (Lake et al, 2016; Tasic et al, 2016; Zeisel et al, 2015), hippocampus (Zeisel et al, 2015), and striatum (Gokce et al, 2016) has been cataloged to an unprecedented level, the cost and effort of profiling large numbers of single cells by conventional scRNA-seq methods prevent its broader application to highly complex brain regions, such as the hypothalamus.…”

“…While cell diversity in the cerebral cortex (Lake et al, 2016; Tasic et al, 2016; Zeisel et al, 2015), hippocampus (Zeisel et al, 2015), and striatum (Gokce et al, 2016) has been cataloged to an unprecedented level, the cost and effort of profiling large numbers of single cells by conventional scRNA-seq methods prevent its broader application to highly complex brain regions, such as the hypothalamus. To overcome this challenge, cost-efficient scRNA-seq methods have been developed to achieve high-throughput parallel analysis (Klein et al, 2015; Macosko et al, 2015), making scRNA-seq analysis of complex brain regions possible.…”

Restoration of Physiological Expression of 5-HT6 Receptor into the Primary Cilia of Null Mutant Neurons Lengthens Both Primary Cilia and Dendrites

“…This culturing method was adapted from previously described methods (Lesiak et al, 2015;Brodsky et al, 2017) analysis (Gokce et al, 2016). Cultures were maintained at 37ºC under 5% CO2 from DIV0 until homogenization or fixation.…”