Evidence map›Paper›PMID 21877920›Full record

ArticleHuman gene therapy2012

Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells.

A Sánchez-Danés, A Consiglio, Y Richaud, I Rodríguez-Pizà, B Dehay, M Edel, J Bové, M Memo, M Vila, A Raya and 1 more

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

67 citing papers in PubMed, 125 citations in OpenAlex.

  1. Review
  2. Properties and Application of Pseudotyped Lentiviral Vectors.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Reporter Alleles in hiPSCs: Visual Cues on Development and Disease.International journal of molecular sciences · 2024
    Review
  7. Article
  8. Article
  9. Review
  10. Article
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  15. Review
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  18. Article
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7 more citing papers are in PubMed but not listed here.

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

11 authors at 7 institutions in 3 countries.

A Sánchez-Danés1 Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
A Consiglio
Y Richaud
I Rodríguez-Pizà
B Dehay
M Edel
J Bové
M Memo
M Vila
A Raya
J C Izpisua Belmonte
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine · ESInstitut de Biomedicina de la Universitat de BarcelonaVall d'Hebron Institut de Recerca · ESCenter of Regenerative Medicine in Barcelona · ESInstitució Catalana de Recerca i Estudis Avançats · ESSalk Institute for Biological Studies · USUniversity of Brescia · IT

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
6 · The paper itself

Abstract

Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) offer great hope for in vitro modeling of Parkinson's disease (PD), as well as for designing cell-replacement therapies. To realize these opportunities, there is an urgent need to develop efficient protocols for the directed differentiation of hESC/iPSC into dopamine (DA) neurons with the specific characteristics of the cell population lost to PD, i.e., A9-subtype ventral midbrain DA neurons. Here we use lentiviral vectors to drive the expression of LMX1A, which encodes a transcription factor critical for ventral midbrain identity, specifically in neural progenitor cells. We show that clonal lines of hESC engineered to contain one or two copies of this lentiviral vector retain long-term self-renewing ability and pluripotent differentiation capacity. Greater than 60% of all neurons generated from LMX1A-engineered hESC were ventral midbrain DA neurons of the A9 subtype, compared with ∼10% in green fluorescent protein-engineered controls, as judged by specific marker expression and functional analyses. Moreover, DA neuron precursors differentiated from LMX1A-engineered hESC were able to survive and differentiate when grafted into the brain of adult mice. Finally, we provide evidence that LMX1A overexpression similarly increases the yield of DA neuron differentiation from human iPSC. Taken together, our data show that stable genetic engineering of hESC/iPSC with lentiviral vectors driving controlled expression of LMX1A is an efficient way to generate enriched populations of human A9-subtype ventral midbrain DA neurons, which should prove useful for modeling PD and may be helpful for designing future cell-replacement strategies.

Indexed as

AnimalsCell CountCell DifferentiationCells, CulturedDopaminergic NeuronsEmbryonic Stem CellsGenetic EngineeringGenetic VectorsGreen Fluorescent ProteinsHumansInduced Pluripotent Stem CellsLentivirusLIM-Homeodomain ProteinsMesencephalonMiceMice, NudeGreen Fluorescent ProteinsLIM-Homeodomain ProteinsLMX1A protein, humanTranscription Factors

Identifiers

PMID21877920
PMCPMC3472681
OpenAlexW2076952677

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.