Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease

Output Details

Preprint May 4, 2023

Published February 21, 2023

The brain is spatially organized and contains unique cell types, each performing diverse functions and exhibiting differential susceptibility to neurodegeneration. This is exemplified in Parkinson’s disease with the preferential loss of dopaminergic neurons of the substantia nigra pars compacta. Using a Parkinson’s transgenic model, we conducted a single-cell spatial transcriptomic and dopaminergic neuron translatomic analysis of young and old mouse brains. Through the high resolving capacity of single-cell spatial transcriptomics, we provide a deep characterization of the expression features of dopaminergic neurons and 27 other cell types within their spatial context, identifying markers of healthy and aging cells, spanning Parkinson’s relevant pathways. We integrate gene enrichment and genome-wide association study data to prioritize putative causative genes for disease investigation, identifying CASR as a regulator of dopaminergic calcium handling. These datasets represent the largest public resource for the investigation of spatial gene expression in brain cells in health, aging, and disease.
Tags
  • 10X Genomics
  • Aging
  • Dopaminergic neurons
  • hiPSCs (Human induced pluripotent stem cells)
  • Immunofluorescence
  • Mouse
  • Original Research
  • RNA-seq
  • Single-cell
  • Spatial transcriptomics

Meet the Authors

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    Peter kilfeather

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    Jia Hui Khoo

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    Katherina Wagner

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    Han Liang

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    Maria Claudia Caiazza

    Key Personnel: Team Cragg

    University of Oxford

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    Yanru An

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    Xingju Zhang

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    Xiaoyan Chen

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    Natalie Connor-Robson

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    Zhouchun Shang

  • Richard Wade-Martins, PhD

    Co-PI (Core Leadership): Team Cragg

    University of Oxford