The loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) is a hallmark of Parkinson's disease (PD). This study used a protocol to enrich and transcriptionally profile DA neurons from PD patients and controls, analyzing 387,483 nuclei (22,048 DA neurons). Ten DA neuron populations were identified and spatially localized. A subtype marked by *AGTR1* expression, located in the ventral SNpc, showed high susceptibility to loss in PD and upregulation of TP53 and NR2F2 targets. This vulnerable population was enriched for heritable PD risk, highlighting cell-intrinsic mechanisms in differential vulnerability.
Publisher
Nature Neuroscience
Published On
May 05, 2022
Authors
Tushar Kamath, Abdulraouf Abdulraouf, S. J. Burris, Jonah Langlieb, Vahid Gazestani, Naeem M. Nadaf, Karol Balderrama, Charles Vanderburg, Evan Z. Macosko
Tags
dopamine neurons
Parkinson's disease
substantia nigra
AGTR1 expression
cell-intrinsic mechanisms
transcriptional profiling
PD risk
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