Evidence map›Paper›PMID 32154672›Full record

ArticleStem cells translational medicine2020

Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells.

Malvin Jefri, Scott Bell, Huashan Peng, Nuwan Hettige, Gilles Maussion, Vincent Soubannier, Hanrong Wu, Heika Silveira, Jean-Francois Theroux, Luc Moquin and 13 more

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 30 citations in OpenAlex.

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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

23 authors at 4 institutions in 2 countries.

Malvin JefriPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Scott BellPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Huashan PengPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Nuwan HettigePsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Gilles MaussionDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada.
Vincent SoubannierDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada.
Hanrong WuPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Heika SilveiraPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Jean-Francois TherouxPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Luc MoquinDepartment of Psychiatry, McGill University and Douglas Hospital Research Institute, Montreal, Quebec, Canada.
Xin ZhangPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Zahia AouabedPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Jeyashree KrishnanInstitute for Computational Biomedicine, Aachen University, Aachen, Germany.
Liam A O'LearyDepartment of Psychiatry, McGill University and Douglas Hospital Research Institute, Montreal, Quebec, Canada.
Lilit Antonyan
Ying ZhangPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Vincent McCartyPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.
Naguib MechawarDepartment of Psychiatry, McGill University and Douglas Hospital Research Institute, Montreal, Quebec, Canada.
Alain GrattonDepartment of Psychiatry, McGill University and Douglas Hospital Research Institute, Montreal, Quebec, Canada.
Andreas SchuppertInstitute for Computational Biomedicine, Aachen University, Aachen, Germany.
Thomas M DurcanDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada.
Edward A FonDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada.
Carl ErnstPsychiatric Genetics Group, McGill University, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0002-2959-221X
Douglas Mental Health University Institute · CAMcGill University · CAMontreal Neurological Institute and Hospital · CARWTH Aachen University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Making high-quality dopamine (DA)-producing cells for basic biological or small molecule screening studies is critical for the development of novel therapeutics for disorders of the ventral midbrain. Currently, many ventral midbrain assays have low signal-to-noise ratio due to low levels of cellular DA and the rate-limiting enzyme of DA synthesis, tyrosine hydroxylase (TH), hampering discovery efforts. Using intensively characterized ventral midbrain cells derived from human skin, which demonstrate calcium pacemaking activity and classical electrophysiological properties, we show that an L-type calcium agonist can significantly increase TH protein levels and DA content and release. Live calcium imaging suggests that it is the immediate influx of calcium occurring simultaneously in all cells that drives this effect. Genome-wide expression profiling suggests that L-type calcium channel stimulation has a significant effect on specific genes related to DA synthesis and affects expression of L-type calcium receptor subunits from the CACNA1 and CACNA2D families. Together, our findings provide an advance in the ability to increase DA and TH levels to improve the accuracy of disease modeling and small molecule screening for disorders of the ventral midbrain, including Parkinson's disease.

Indexed as

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl esterCalciumCalcium Channels, L-TypeCell DifferentiationCell LineCell ShapeDopamineDopaminergic NeuronsElectrophysiological PhenomenaHepatocyte Nuclear Factor 3-betaHumansMesencephalonNeural Stem CellsTranscriptomeTyrosine 3-Monooxygenase3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl esterCalciumCalcium Channels, L-TypeDopamineHepatocyte Nuclear Factor 3-betaTyrosine 3-Monooxygenasecell biologyinduced pluripotent stem cells (iPSCs)nervous systemneural differentiationneural induction

Identifiers

PMID32154672
PMCPMC7214648
OpenAlexW3011254981

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.