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

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Title: Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson's disease.
Authors: Kamath, Tushar (AUTHOR), Abdulraouf, Abdulraouf (AUTHOR), Burris, S. J. (AUTHOR), Langlieb, Jonah (AUTHOR), Gazestani, Vahid (AUTHOR), Nadaf, Naeem M. (AUTHOR), Balderrama, Karol (AUTHOR), Vanderburg, Charles (AUTHOR), Macosko, Evan Z. (AUTHOR)
Source: Nature Neuroscience. May2022, Vol. 25 Issue 5, p588-595. 8p.
Abstract: 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 AGTR1 and spatially confined to the ventral tier of SNpc, was highly susceptible to loss in PD and showed the strongest upregulation of targets of TP53 and NR2F2, 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. The authors used single-cell genomics to profile thousands of human dopamine neurons and identify one uniquely Parkinson's disease-susceptible population, which was enriched for genetic risk for Parkinson's disease. [ABSTRACT FROM AUTHOR]
Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson's disease.
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  Data: <searchLink fieldCode="AR" term="%22Kamath%2C+Tushar%22">Kamath, Tushar</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Abdulraouf%2C+Abdulraouf%22">Abdulraouf, Abdulraouf</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Burris%2C+S%2E+J%2E%22">Burris, S. J.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Langlieb%2C+Jonah%22">Langlieb, Jonah</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gazestani%2C+Vahid%22">Gazestani, Vahid</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nadaf%2C+Naeem+M%2E%22">Nadaf, Naeem M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Balderrama%2C+Karol%22">Balderrama, Karol</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vanderburg%2C+Charles%22">Vanderburg, Charles</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Macosko%2C+Evan+Z%2E%22">Macosko, Evan Z.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. May2022, Vol. 25 Issue 5, p588-595. 8p.
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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 AGTR1 and spatially confined to the ventral tier of SNpc, was highly susceptible to loss in PD and showed the strongest upregulation of targets of TP53 and NR2F2, 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. The authors used single-cell genomics to profile thousands of human dopamine neurons and identify one uniquely Parkinson's disease-susceptible population, which was enriched for genetic risk for Parkinson's disease. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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