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

Tushar Kamath, Abdulraouf Abdulraouf, S. J. Burris, Jonah Langlieb, Vahid Gazestani, Naeem M. Nadaf, Karol Balderrama, Charles Vanderburg, Evan Z. Macosko

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.

Datasets

1. Human Oligodendrocytes 10x scRNA-seq
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Olig_PLXDC2_SFRP158207 cells
Olig_ENPP6_LUCAT137842 cells
Olig_PLXDC228033 cells
Olig_PLXDC2_KCNAB125819 cells
Olig_ENPP6_EMILIN218750 cells
Olig_ENPP6_ACTN26731 cells
Olig_PLXDC2_KCNK103433 cells
Preview
Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
2. Human Nurr-Negative Nuclei 10x scRNA-seq
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author_cell_type
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nonda103436 cells
da661 cells
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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
3. Human Non-DA Neurons 10x scRNA-seq
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Inh_PRLR_RP11-384J4.216200 cells
Ex_MYO5B11050 cells
Ex_EBF2_CTC-552D5.18024 cells
Ex_LAMP5_NTNG27808 cells
Ex_LAMP5_BAIAP37032 cells
Inh_SIX35528 cells
Ex_VWA5B1_CALB15034 cells
Inh_PAX5_CCBE14976 cells
Inh_IGFBP54944 cells
Ex_OPRD13734 cells
Ex_POSTN3492 cells
Ex_PPP1R1C3058 cells
Ex_SATB22797 cells
Ex_CYP2J22730 cells
Inh_OTX2_CASR2377 cells
Inh_PAX5_VCAN1382 cells
Inh_INHBA1313 cells
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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
4. Human Nurr-Positive Nuclei 10x scRNA-seq
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nonda64139 cells
da16437 cells
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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
5. Human Astrocytes 10x scRNA-seq
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Astro_GJB6_OXTR15747 cells
Astro_CYP4F126763 cells
Astro_GUCY1A23143 cells
Astro_SIDT12920 cells
Astro_GLYATL21723 cells
Astro_VIM_TNFSRF12A1486 cells
Astro_SERPINA3555 cells
Astro_GBP2_SPOCD1505 cells
Astro_VIM_LHX2419 cells
Ependyma_ZBBX245 cells
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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
6. Human Human Microglia 10x scRNA-seq
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MG_TSPO_VIM8361 cells
MG_CECR2_FGL18274 cells
MG_OPRM16115 cells
MG_GPNMB_SULT1C22093 cells
MG_GPNMB_SUSD11780 cells
MG_FOSL21511 cells
MG_SPON11494 cells
Macro_CD200R11230 cells
MG_GPNMB_LPL1186 cells
MG_MGAM423 cells
MG_CCL3354 cells
MG_MKI67220 cells
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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
7. Human DA Neurons 10x scRNA-seq
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SOX6_AGTR18498 cells
SOX6_PART12646 cells
CALB1_CALCR2479 cells
SOX6_DDT2414 cells
SOX6_GFRA21589 cells
CALB1_PPP1R171358 cells
CALB1_CRYM_CCDC68931 cells
CALB1_GEM884 cells
CALB1_RBP4763 cells
CALB1_TRHR486 cells
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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
8. Human Endothelial cells 10x scRNA-seq
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Endo_DCN_ABCC94769 cells
Endo_IL27RA4408 cells
Endo_COL6A32960 cells
Endo_NOTCH3_PLK21134 cells
Endo_SNTG2770 cells
Endo_SLIT3702 cells
Endo_MET160 cells
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Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
9. Human OPC Cells 10x scRNA-seq
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OPC_CACNG412199 cells
OPC_HOXD3503 cells
OPC_KIAA0040489 cells
OPC_ADM390 cells
OPC_MDFI110 cells
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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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Source data

https://cellxgene.cziscience.com/collections/b0f0b447-ac37-45b0-b1bf-5c0b7d871120

Alias names

GSE178265, SCP1768, PMID35513515, PMC9076534

Cite this study

Kamath, T., Abdulraouf, A., Burris, S.J., Langlieb, J., Gazestani, V., Nadaf, N.M., Balderrama, K., Vanderburg, C. and Macosko, E.Z., 2022. Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease. Nature neuroscience, 25(5), pp.588-595. https://doi.org/10.1038/s41593-022-01061-1