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.