Evidence map›Paper›PMID 34305528›Full record

ArticleFrontiers in molecular neuroscience2021

Spatial RNA Sequencing Identifies Robust Markers of Vulnerable and Resistant Human Midbrain Dopamine Neurons and Their Expression in Parkinson's Disease.

Julio Aguila, Shangli Cheng, Nigel Kee, Ming Cao, Menghan Wang, Qiaolin Deng, Eva Hedlund

Open access · goldAbstract read
In one paragraph

Article in Frontiers in molecular neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. KChIP4a is a Biophysical Amplifier of Inhibition in Atypical Dopamine Neurons and Controls Learning from Negative Prediction Errors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
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  11. New Multiomic Studies Shed Light on Cellular Diversity and Neuronal Susceptibility in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025
    Review
  12. Proteomic insights into the biology of dopaminergic neurons.Frontiers in molecular neuroscience · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Julio AguilaDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Shangli ChengDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Nigel KeeDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Ming CaoDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Menghan WangDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Qiaolin DengDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Eva HedlundDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Karolinska Institutet · SEKarolinska University Hospital · SEStockholm University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Defining transcriptional profiles of substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopamine neurons is critical to understanding their differential vulnerability in Parkinson's Disease (PD). Here, we determine transcriptomes of human SNc and VTA dopamine neurons using LCM-seq on a large sample cohort. We apply a bootstrapping strategy as sample input to DESeq2 and identify 33 stably differentially expressed genes (DEGs) between these two subpopulations. We also compute a minimal sample size for identification of stable DEGs, which highlights why previous reported profiles from small sample sizes display extensive variability. Network analysis reveal gene interactions unique to each subpopulation and highlight differences in regulation of mitochondrial stability, apoptosis, neuronal survival, cytoskeleton regulation, extracellular matrix modulation as well as synapse integrity, which could explain the relative resilience of VTA dopamine neurons. Analysis of PD tissues showed that while identified stable DEGs can distinguish the subpopulations also in disease, the SNc markers SLIT1 and ATP2A3 were down-regulated and thus appears to be biomarkers of disease. In summary, our study identifies human SNc and VTA marker profiles, which will be instrumental for studies aiming to modulate dopamine neuron resilience and to validate cell identity of stem cell-derived dopamine neurons.

Indexed as

human midbrain dopamine neuronslaser microdissectionParkinson’s diseaseRNA sequencingspatial transcriptomicssubstantia nigra compactaventral tegmental area

Identifiers

PMID34305528
PMCPMC8297217
OpenAlexW3179493165

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.