Evidence map›Paper›PMID 17234989›Full record

ArticleStem cells (Dayton, Ohio)2007

Selection of embryonic stem cell-derived enhanced green fluorescent protein-positive dopamine neurons using the tyrosine hydroxylase promoter is confounded by reporter gene expression in immature cell populations.

Eva Hedlund, Jan Pruszak, Andrew Ferree, Angel Viñuela, Sunghoi Hong, Ole Isacson, Kwang-Soo Kim

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 65 citations in OpenAlex.

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  14. Review
  15. Microfluidics for cell separation.Medical & biological engineering & computing · 2010
    Review
  16. Stem cell-based neuroprotective and neurorestorative strategies.International journal of molecular sciences · 2010
    Review
  17. High-efficiency transient transduction of human embryonic stem cell-derived neurons with baculoviral vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2009
    Article
  18. Upping the ante: recent advances in direct reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2009
    Review
  19. Article
  20. Article
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 2 institutions in 1 country.

Eva HedlundUdall Parkinson's Disease Research Center for Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
Jan Pruszak
Andrew Ferree
Angel Viñuela
Sunghoi Hong
Ole Isacson
Kwang-Soo Kim
McLean Hospital · USHarvard University · US

Funding

Transplantation of ES Cell-derived DA Neurons into PD Primate ModelsP50NS039793 · NINDS · MC LEAN HOSPITAL (BELMONT, MA) · PI ISACSON, OLE · 1999 to 2010
$16.3M
Functional Roles of Nurr1 for Midbrain Dopamine Neurons in Health and DiseaseR01NS084869 · NINDS · MCLEAN HOSPITAL · PI KIM, KWANG-SOO · 2014 to 2018
$1.7M
NINDS NIH HHS P50 NS039793NINDS NIH HHS P50 NS39793NINDS NIH HHS R01 NS084869
6 · The paper itself

Abstract

Transplantation of mouse embryonic stem (mES) cells can restore function in Parkinson disease models, but can generate teratomas. Purification of dopamine neurons derived from embryonic stem cells by fluorescence-activated cell sorting (FACS) could provide a functional cell population for transplantation while eliminating the risk of teratoma formation. Here we used the tyrosine hydroxylase (TH) promoter to drive enhanced green fluorescent protein (eGFP) expression in mES cells. First, we evaluated 2.5-kilobase (kb) and 9-kb TH promoter fragments and showed that clones generated using the 9-kb fragment produced significantly more eGFP+/TH+ neurons. We selected the 9-kb TH clone with the highest eGFP/TH overlap for further differentiation, FACS, and transplantation experiments. Grafts contained large numbers of eGFP+ dopamine neurons of an appropriate phenotype. However, there were also numerous eGFP+ cells that did not express TH and did not have a neuronal morphology. In addition, we found cells in the grafts representing all three germ layers. Based on these findings, we examined the expression of stem cell markers in our eGFP+ population. We found that a majority of eGFP+ cells were stage-specific embryonic antigen-positive (SSEA-1+) and that the genetically engineered clones contained more SSEA-1+ cells after differentiation than the original D3 mES cells. By negative selection of SSEA-1, we could isolate a neuronal eGFP+ population of high purity. These results illustrate the complexity of using genetic selection to purify mES cell-derived dopamine neurons and provide a comprehensive analysis of cell selection strategies based on tyrosine hydroxylase expression. Disclosure of potential conflicts of interest is found at the end of this article.

Indexed as

Genes, ReporterAnimalsCell DifferentiationCell ProliferationDopamineEmbryonic Stem CellsFlow CytometryGene ExpressionGreen Fluorescent ProteinsLewis X AntigenMiceMice, Inbred C57BLNeuronsPromoter Regions, GeneticRatsRats, Sprague-DawleyDopamineenhanced green fluorescent proteinGreen Fluorescent ProteinsLewis X AntigenTyrosine 3-Monooxygenase

Identifiers

PMID17234989
PMCPMC2614084
OpenAlexW2161301993

What OpenQuestion holds

Textmetadata
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.