Evidence map›Paper›PMID 19672298›Full record

ArticlePloS one2009

A novel combination of factors, termed SPIE, which promotes dopaminergic neuron differentiation from human embryonic stem cells.

Tandis Vazin, Kevin G Becker, Jia Chen, Charles E Spivak, Carl R Lupica, Yongqing Zhang, Lila Worden, William J Freed

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 94 citations in OpenAlex.

  1. Review
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  9. Review
  10. Stem cell colony interspacing effect on differentiation to neural cells.Journal of tissue engineering and regenerative medicine · 2018
    Article
  11. Article
  12. Article
  13. Time-Dependent, HIV-Tat-Induced Perturbation of Human NeuronsFrontiers in molecular neuroscience · 2017
    Article
  14. Article
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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

8 authors at 3 institutions in 2 countries.

Tandis VazinCellular Neurobiology Research Branch, Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), NIH, DHHS, Baltimore, MD, USA. vazint@mail.nih.gov
Kevin G Becker
Jia Chen
Charles E Spivak
Carl R Lupica
Yongqing Zhang
Lila Worden
William J Freed
National Institutes of Health · USInstitute on Aging · USNational Institute on Drug Abuse · US

Funding

Analysis of complex biological systems by microarray based gene expressionZICAG000616 · NIA · NATIONAL INSTITUTE ON AGING · PI DE, SUPRIYO · 2009 to 2025
$15.5M
Human Embryonic Stem Cells: Characterization and Dopaminergic DifferentiationZIADA000472 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI FREED, WILLIAM · 2009 to 2015
$7.7M
Physiology and Pharmacology of Brain Reward CircuitsZIADA000457 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI LUPICA, CARL · 2009 to 2021
$7.4M
Human Embryonic Stem Cells:Characterization/DopaminergicZ01DA000472 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI FREED, WILLIAM · 2004 to 2008
$1.8M
Analysis of complex biological systems by microarray based gene expressionZ01AG000616 · NIA · NATIONAL INSTITUTE ON AGING · PI BECKER, KEVIN · 2008 to 2008
$886k
6 · The paper itself

Abstract

backgroundStromal-Derived Inducing Activity (SDIA) is one of the most efficient methods of generating dopaminergic (DA) neurons from embryonic stem cells (ESC). DA neuron induction can be achieved by co-culturing ESC with the mouse stromal cell lines PA6 or MS5. The molecular nature of this effect, which has been termed "SDIA" is so far unknown. Recently, we found that factors secreted by PA6 cells provided lineage-specific instructions to induce DA differentiation of human ESC (hESC). METHODOLOGY/PRINCIPAL

findingsIn the present study, we compared PA6 cells to various cell lines lacking the SDIA effect, and employed genome expression analysis to identify differentially-expressed signaling molecules. Among the factors highly expressed by PA6 cells, and known to be associated with CNS development, were stromal cell-derived factor 1 (SDF-1/CXCL12), pleiotrophin (PTN), insulin-like growth factor 2 (IGF2), and ephrin B1 (EFNB1). When these four factors, the combination of which was termed SPIE, were applied to hESC, they induced differentiation to TH-positive neurons in vitro. RT-PCR and western blot analysis confirmed the expression of midbrain specific markers, including engrailed 1, Nurr1, Pitx3, and dopamine transporter (DAT) in cultures influenced by these four molecules. Electrophysiological recordings showed that treatment of hESC with SPIE induced differentiation of neurons that were capable of generating action potentials and forming functional synaptic connections. CONCLUSIONS/SIGNIFICANCE: The combination of SDF-1, PTN, IGF2, and EFNB1 mimics the DA phenotype-inducing property of SDIA and was sufficient to promote differentiation of hESC to functional midbrain DA neurons. These findings provide a method for differentiating hESC to form DA neurons, without a requirement for the use of animal-derived cell lines or products.

Indexed as

AnimalsBlotting, WesternCarrier ProteinsCell DifferentiationChemokine CXCL12Coculture TechniquesCytokinesDopamineEmbryonic Stem CellsEphrin-B1HumansInsulin-Like Growth Factor IIMiceNeuronsOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionCarrier ProteinsChemokine CXCL12CytokinesDopamineEphrin-B1Insulin-Like Growth Factor IIpleiotrophin

Identifiers

PMID19672298
PMCPMC2719871
OpenAlexW2037562977

What OpenQuestion holds

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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.