Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2^G2019S model of Parkinson's disease.

ABSTRACT: Several studies have revealed that midbrain dopamine (DA) neurons, even within a single neuroanatomical area, display heterogeneous properties. In parallel, studies using singlecell profiling techniques have begun to cluster DA neurons into subtypes based on their molecular signatures. Recent work has shown that molecularly defined DA subtypes within the substantia nigra (SNc) display distinctive anatomic and functional properties, and differential vulnerability in Parkinson's disease (PD). Based on these provocative results, a granular understanding of these putative subtypes and their alterations in PD models, is imperative. We developed an optimized pipeline for single-nuclear RNA sequencing (snRNA-seq) and generated a high-resolution hierarchically organized map revealing 20 molecularl

SUBMITTER: Gaertner Z 

PROVIDER: S-EPMC12068872 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature