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Series GSE178265 Query DataSets for GSE178265
Status Public on Jun 16, 2021
Title A molecular census of midbrain dopaminergic neurons in Parkinsons disease
Organisms Macaca mulatta; Homo sapiens; Rattus norvegicus; Tupaia belangeri
Experiment type Expression profiling by high throughput sequencing
Summary Midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) project widely throughout the central nervous system, playing critical roles in voluntary movements, reward processing, and working memory. Many of these neurons are highly sensitive to neurodegeneration in Parkinson’s Disease (PD), and their loss correlates strongly with the pathognomonic symptoms. To characterize these populations molecularly, we developed a protocol to enrich and transcriptionally profile DA neuron nuclei from postmortem human SNpc of both PD patients and matched controls. We identified a total of ten distinct populations, including one that was primate-specific. A single subtype, marked by the gene AGTR1, was highly susceptible to degeneration, and was enriched for expression of genes associated with PD in genetic studies, suggesting many risk loci act within this subtype to influence its neurodegeneration. The AGTR1 subtype also showed the strongest upregulation of TP53 and its downstream targets, nominating a potential pathway of degeneration in vivo. The transcriptional characterization of differentially disease-vulnerable DA neurons in the SNpc will inform the development of laboratory models, enable the nomination of novel disease biomarkers, and guide further studies of pathogenic disease mechanisms.
Overall design Characterization and annotation of single nuclei transcriptomes from postmortem human, rat, macaque, and tree shrew substantia nigra and human caudate nucleus.

>>>Submitter states that raw data for human samples will be submitted to dbGaP due to patient privacy concerns<<<
Contributor(s) Kamath T, Abdul A, Burris SJ, Nadaf N, Gazestani V, Vanderburg C, Macosko E
Citation(s) 35513515
Submission date Jun 15, 2021
Last update date May 25, 2022
Contact name Evan Macosko
Organization name Broad Institute
Street address 75 Ames St, Broad Institute
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (4)
GPL20084 Illumina NextSeq 500 (Rattus norvegicus)
GPL21120 Illumina NextSeq 500 (Macaca mulatta)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (101)
GSM5386624 pPDsTreeShrewrSNxixd200314x
GSM5386625 pPDsRatrSNxixd200314x
GSM5386626 pPDsMMrSNxiNIH1d200516DAPI
BioProject PRJNA738165
SRA SRP324163

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Supplementary file Size Download File type/resource
GSE178265_Homo_bcd.tsv.gz 2.6 Mb (ftp)(http) TSV
GSE178265_Homo_features.tsv.gz 288.4 Kb (ftp)(http) TSV
GSE178265_Homo_matrix.mtx.gz 4.7 Gb (ftp)(http) MTX
GSE178265_Macaca_bcd.tsv.gz 7.1 Kb (ftp)(http) TSV
GSE178265_Macaca_features.tsv.gz 132.6 Kb (ftp)(http) TSV
GSE178265_Macaca_matrix.mtx.gz 25.3 Mb (ftp)(http) MTX
GSE178265_Rattus_bcd.tsv.gz 6.9 Kb (ftp)(http) TSV
GSE178265_Rattus_features.tsv.gz 101.5 Kb (ftp)(http) TSV
GSE178265_Rattus_matrix.mtx.gz 9.3 Mb (ftp)(http) MTX
GSE178265_Tupaia_bcd.tsv.gz 6.2 Kb (ftp)(http) TSV
GSE178265_Tupaia_features.tsv.gz 80.2 Kb (ftp)(http) TSV
GSE178265_Tupaia_matrix.mtx.gz 5.9 Mb (ftp)(http) MTX
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Processed data are available on Series record

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