ArticleAnnals of neurology2020
Human-Specific Transcriptome of Ventral and Dorsal Midbrain Dopamine Neurons.
Article in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- New Multiomic Studies Shed Light on Cellular Diversity and Neuronal Susceptibility in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Article
- The Formation and Function of the VTA Dopamine System.International journal of molecular sciences · 2024Review
- Common mitochondrial deletions in RNA-Seq: evaluation of bulk, single-cell, and spatial transcriptomic datasets.Communications biology · 2024Article
- Is There a Natural, Non-addictive, and Non-anti-reward, Safe, Gene-based Solution to Treat Reward Deficiency Syndrome? KB220 Variants vs GLP-1 Analogs.Journal of addiction psychiatry · 2024Article
- Nigral transcriptomic profiles in Engrailed-1 hemizygous mouse models of Parkinson's disease reveal upregulation of oxidative phosphorylation-related genes associated with delayed dopaminergic neurodegeneration.Frontiers in aging neuroscience · 2024Article
- Expression Pattern of Trace Amine-Associated Receptors during Differentiation of Human Pluripotent Stem Cells to Dopaminergic Neurons.International journal of molecular sciences · 2023Article
- Insights into Neurodegeneration in Parkinson's Disease from Single-Cell and Spatial Genomics.Movement disorders : official journal of the Movement Disorder Society · 2023Article
- Development, wiring and function of dopamine neuron subtypes.Nature reviews. Neuroscience · 2023Review
- Physiological and Pathological Functions of Neuronal Hemoglobin: A Key Underappreciated Protein in Parkinson's Disease.International journal of molecular sciences · 2022Review
- β-Aminoisobutyric acid, L-BAIBA, protects PC12 cells from hydrogen peroxide-induced oxidative stress and apoptosis via activation of the AMPK and PI3K/Akt pathway.IBRO neuroscience reports · 2022Article
- Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson's disease.Nature neuroscience · 2022Article
- Developmental pathways linked to the vulnerability of adult midbrain dopaminergic neurons to neurodegeneration.Frontiers in molecular neuroscience · 2022Review
- Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.Cell reports · 2021Article
- Article
- Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease.Biomedicines · 2021Review
- Spatial RNA Sequencing Identifies Robust Markers of Vulnerable and Resistant Human Midbrain Dopamine Neurons and Their Expression in Parkinson's Disease.Frontiers in molecular neuroscience · 2021Article
- Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson's Disease.Frontiers in cellular neuroscience · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveNeuronal loss in the substantia nigra pars compacta (SNpc) in Parkinson disease (PD) is not uniform, as dopamine neurons from the ventral tier are lost more rapidly than those of the dorsal tier. Identifying the intrinsic differences that account for this differential vulnerability may provide a key for developing new treatments for PD.
methodsHere, we compared the RNA-sequenced transcriptomes of ~100 laser captured microdissected SNpc neurons from each tier from 7 healthy controls.
resultsExpression levels of dopaminergic markers were similar across the tiers, whereas markers specific to the neighboring ventral tegmental area were virtually undetected. After accounting for unwanted sources of variation, we identified 106 differentially expressed genes (DEGs) between the SNpc tiers. The genes higher in the dorsal/resistant SNpc tier neurons displayed coordinated patterns of expression across the human brain, their protein products had more interactions than expected by chance, and they demonstrated evidence of functional convergence. No significant shared functionality was found for genes higher in the ventral/vulnerable SNpc tier. Surprisingly but importantly, none of the identified DEGs was among the familial PD genes or genome-wide associated loci. Finally, we found some DEGs in opposite tier orientation between human and analogous mouse populations.
interpretationOur results highlight functional enrichments of vesicular trafficking, ion transport/homeostasis and oxidative stress genes showing higher expression in the resistant neurons of the SNpc dorsal tier. Furthermore, the comparison of gene expression variation in human and mouse SNpc populations strongly argues for the need of human-focused omics studies. ANN NEUROL 2020;87:853-868.
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Registered trials
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