Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
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説明
<jats:title>Abstract</jats:title><jats:p>The loss of dopamine (DA) neurons within the substantia nigra pars compacta (SNpc) is a defining pathological hallmark of Parkinson’s disease (PD). Nevertheless, the molecular features associated with DA neuron vulnerability have not yet been fully identified. Here, we developed a protocol to enrich and transcriptionally profile DA neurons from patients with PD and matched controls, sampling a total of 387,483 nuclei, including 22,048 DA neuron profiles. We identified ten populations and spatially localized each within the SNpc using Slide-seq. A single subtype, marked by the expression of the gene<jats:italic>AGTR1</jats:italic>and spatially confined to the ventral tier of SNpc, was highly susceptible to loss in PD and showed the strongest upregulation of targets of<jats:italic>TP53</jats:italic>and<jats:italic>NR2F2</jats:italic>, nominating molecular processes associated with degeneration. This same vulnerable population was specifically enriched for the heritable risk associated with PD, highlighting the importance of cell-intrinsic processes in determining the differential vulnerability of DA neurons to PD-associated degeneration.</jats:p>
収録刊行物
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- Nature Neuroscience
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Nature Neuroscience 25 (5), 588-595, 2022-05
Springer Science and Business Media LLC
