Description

Single-cell RNA-Seq analysis of striatal medium spiny neurons reveals novel subtypes

Jim Notwell*, Dino Leone*, Sasha Sharma, Amy Nguyen, and Thomas Portmann

Circuit Therapeutics Inc., 1505 O’Brien Drive, Menlo Park, CA 94025, USA

*equal contributors

Single-cell RNA sequencing (scRNA-Seq) has advanced our understanding of heterogeneous tissues comprising the brain. We investigated medium spiny neurons (MSNs) of the striatum, a group of GABAergic projection neurons separated into two types, D1-type and D2-type MSNs, based on their expression of D1 and D2 dopamine receptors. Striatal MSNs have long been appreciated for their pivotal role in basal ganglia circuitry, implicating them in a range of CNS diseases. We analyzed scRNA-Seq data from our own experiments, as well as public sources, using a variety of tools. We identified robust clusters corresponding to different subtypes of D1-type and D2-type MSNs, thus suggesting the existence of regional, functional and circuit-specific transcriptional signatures. We further identified modules of genes characteristic of these subgroups and based on these, established relationships between anatomical subdomains of the striatum as well as transitional cell types/states.