Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease
Peter Kilfeather,
Jia Hui Khoo,
Katherina Wagner,
Han Liang,
Maria Claudia Caiazza,
Yanru An,
Xingju Zhang,
Xiaoyan Chen,
Natalie Connor-Robson,
Zhouchun Shang,
Richard Wade-Martins
Affiliations
Peter Kilfeather
Oxford Parkinson’s Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, USA
Jia Hui Khoo
BGI Research, 49276 Riga, Latvia
Katherina Wagner
Oxford Parkinson’s Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK
Han Liang
BGI Research, 49276 Riga, Latvia
Maria Claudia Caiazza
Oxford Parkinson’s Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, USA
Yanru An
BGI Research, 49276 Riga, Latvia
Xingju Zhang
BGI Research, 49276 Riga, Latvia
Xiaoyan Chen
BGI Research, 49276 Riga, Latvia
Natalie Connor-Robson
Oxford Parkinson’s Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK
Oxford Parkinson’s Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, USA; Corresponding author
Summary: 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.
