A molecular atlas of cell-type specific signatures in the parkinsonian striatum

By Marta Graziano, MSc, Ioannis Mantas, MD, PhD, Yuvarani Masarapu, Solène Frapard, Raquel Garza, PhD, Anita Adami, MSc, Shaline Fazal, PhD, Annelies Quaegebeur, MD, PhD, Roger Barker, PhD, Johan Jakobsson, PhD, Stefania Giacomello and Konstantinos (Dinos) Meletis, PhD
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Output Details

Description
The progressive degeneration of dopaminergic projections to the striatum is a key disease mechanism in Parkinson’s disease (PD). To define the cellular landscape in the parkinsonian striatum, we mapped the cell-type specific transcriptional landscape in early and progressive PD mouse models and in human PD stages. Our analyses revealed substantial transcriptomic changes across both neuronal and glial populations, with astrocytes and oligodendrocytes exhibiting distinct disease-associated gene expression profiles. Notably, progressive dopamine depletion uncovered differential neuronal vulnerability, identifying eccentric striatal projection neurons (SPNs) and Chst9-expressing direct-pathway SPNs as among the most resilient subtypes in both species. This cross-species resource establishes a comprehensive framework for investigating cell-state dynamics in the parkinsonian striatum and uncovers selectively vulnerable and resistant cell types that can inspire new therapeutic strategies.
Identifier (DOI)
10.1101/2025.09.09.675138
Tags
  • 10X Chromium Single Cell 3'
  • 10X Genomics
  • 6-OHDA
  • Astrocytes
  • Dopaminergic neurons
  • Mouse
  • RNA-seq
  • snRNA-seq (Single-nuclear RNA-seq)
  • Striatum
Team
Team Cragg and Team Jakobsson
Program
Collaborative Research Network
Theme
Circuitry and Brain-Body Interactions Neuro-Immune Interactions

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