Evidence map›Paper›PMID 28096185›Full record

ArticleHuman molecular genetics2017

Transcriptomic profiling of purified patient-derived dopamine neurons identifies convergent perturbations and therapeutics for Parkinson's disease.

Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley and 2 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 2 pooled it
5.0field-weighted citation impact, top 4% 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

49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.

  1. Pooled it
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  17. Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Preventing Parkinson's Disease: An Environmental Agenda.Journal of Parkinson's disease · 2022
    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

12 authors at 2 institutions in 1 country.

Cynthia SandorOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK.
Paul RobertsonOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK.
Charmaine LangOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK.
Andreas HegerMRC Computational Genomics Analysis and Training Program, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Heather BoothOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK.
Jane VowlesJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Lorna WittyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Rory BowdenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Michele HuOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK.
Sally A CowleyJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Richard Wade-MartinsOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK.
Caleb WebberOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, UK.
University of Oxford · GBCentre for Human Genetics · GB

Funding

Medical Research Council G0900747Medical Research Council G0900747 91070Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MC_PC_15065Medical Research Council MC_PC_16034Medical Research Council MC_UP_A320_1004Medical Research Council MC_UU_12021/4Medical Research Council MR/L023784/1Medical Research Council MR/M024962/1Parkinson's UK J-0901Wellcome Trust 090532/Z/09/ZWellcome Trust 092762/Z/10/ZWellcome Trust WT082260/Z/07/ZWellcome Trust WTISSF121302
6 · The paper itself

Abstract

While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes. The PD LRRK2-G2019S associated profile was positively matched with expression changes induced by the Parkinsonian neurotoxin rotenone and opposed by those induced by clioquinol, a compound with demonstrated therapeutic efficacy in multiple PD models. No functional convergence amongst DE genes was observed following a similar comparison using non-purified iPSC-derived DaN-containing populations, with cellular heterogeneity appearing a greater confound than genotypic background.

Indexed as

AutopsyCells, CulturedClioquinolDopamineDopaminergic NeuronsGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MutationParkinson DiseaseRotenoneTranscriptomeClioquinolDopamineLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanRotenone

Identifiers

PMID28096185
PMCPMC5409122
OpenAlexW2579105907

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.