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

Kilfeather, Peter, Khoo, Jia Hui, Wagner, Katherina, Liang, Han, Caiazza, Maria Claudia, An, Yanru, Zhang, Xingju, Chen, Xiaoyan, Connor-Robson, Natalie ORCID: https://orcid.org/0000-0001-8350-6928, Shang, Zhouchun and Wade-Martins, Richard 2024. Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease. Cell Reports 43 (3) , 113784. 10.1016/j.celrep.2024.113784

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Cell Press
ISSN:	2211-1247
Date of First Compliant Deposit:	24 May 2024
Date of Acceptance:	27 January 2024
Last Modified:	28 May 2024 10:45
URI:	https://orca.cardiff.ac.uk/id/eprint/169139

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