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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson's disease

Medicine and Health

Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson's disease

T. Kamath, A. Abdulraouf, et al.

This groundbreaking study by Tushar Kamath, Abdulraouf Abdulraouf, and colleagues reveals crucial insights into the vulnerability of dopamine neurons in Parkinson's disease. By profiling over 387,000 nuclei, researchers uncovered a specific neuron population that is particularly susceptible to degeneration, highlighting significant genetic risks tied to this subtype. This research sheds light on the intrinsic mechanisms behind neuron loss in PD, a critical step towards understanding and treating the disease.

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Playback language: English
Abstract
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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