Human OLIG2-mCherry adenoviral particles

The basal ganglia are known for processing information required for multiple aspects of movement and are part of a network that regulates reward and cognition. The major output nucleus of the basal ganglia is the striatum, and its function depends on neuronal compartments, including the striatum and matrix, which are selectively affected in disease. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), which all share basic molecular characteristics but are divided into subtypes based on the selective expression of receptors, neuropeptides, and other gene families. The researchers performed RNA and ATAC sequencing of postnatal day 3 mouse striatal and matrix cells. Focusing on the striatal compartment, they validated the localization and role of transcription factors and their regulators that were previously not known to be involved in striatal development, including Irx1, Foxf2, Olig2, and Stat1/2. In addition, enhancer function was validated for a striatum-specific open chromatin region located 15Kb downstream of the Olig2 gene. These data and databases provide new tools to dissect and manipulate the networks regulating MSN compartmentalization and differentiation, thereby enabling new approaches to establish MSN subtypes from human iPSCs for disease modeling and drug discovery.

Here, researchers determined whether expression of OLIG2 in mouse primary MSNs promotes striatal MSN maturation (Figure 1a). 96 h after transduction with ADV-OLIG2 mCherry, there was no increase in the number of DARPP-32 immunolabeled DIV9 WT primary striatal neurons. ADV-GFP transduced and non-transduced cells were used as controls. These studies showed that expression of OLIG2 from transduced adenovirus did not increase the number of DARPP-32 immunopositive cells (Figure 1b, c); however, it increased mRNA for striatal markers Oprm1, Foxp2, and Rasgrp1 (Figure 1d), but not the stromal marker Calb1.

Figure 1. Olig2 is expressed in MSNs in vitro and its overexpression promotes their maturation towards a striosome phenotype. (Cirnaru M D, et al. 2020)