Evidence map›Paper›PMID 31317490›Full record

ArticleMolecular neurobiology2020

Neuronal Trans-differentiation by Transcription Factors Ascl1 and Nurr1: Induction of a Dopaminergic Neurotransmitter Phenotype in Cortical GABAergic Neurons.

Anupam Raina, Sameehan Mahajani, Mathias Bähr, Sebastian Kügler

Abstract read
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Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  9. Circuit formation in the adult brain.The European journal of neuroscience · 2022
    Review
  10. Article
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  12. Article
  13. Article
  14. Reprogramming astrocytes into dopaminergic neurons to restore motor dysfunction in ParkinsonZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
    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

4 authors at 1 institution in 1 country.

Anupam RainaDepartment of Neurology, University Medicine Göttingen, Waldweg 33, 37073, Göttingen, Germany.
Sameehan MahajaniDepartment of Neurology, University Medicine Göttingen, Waldweg 33, 37073, Göttingen, Germany.
Mathias BährDepartment of Neurology, University Medicine Göttingen, Waldweg 33, 37073, Göttingen, Germany.
Sebastian KüglerDepartment of Neurology, University Medicine Göttingen, Waldweg 33, 37073, Göttingen, Germany. sebastian.kuegler@med.uni-goettingen.de.ORCID http://orcid.org/0000-0002-5130-2012
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 · DE

Funding

Deutsche Forschungsgemeinschaft CNMPBDeutscher Akademischer Austauschdienst PhD Fellowship
6 · The paper itself

Abstract

Neurons with a desired neurotransmitter phenotype can be differentiated from induced pluripotent stem cells or from somatic cells only through tedious protocols with relatively low yield. Readily available cortical neurons isolated from embryonic rat brain, which have already undergone a complete neuronal differentiation process, might serve as alternative template source. These cultures consist of 85% glutamatergic and 15% GABAergic neurons, and we attempted to trans-differentiate them into dopaminergic neurons. Transcription factors Nurr1, Lmx1A and Pitx3, essential determinants of a dopaminergic cell fate during CNS development, were not sufficient to induce tyrosine hydroxylase expression in a significant number of cells. Combining Nurr1 with the generic neuronal differentiator and re-programming factor Ascl1, however, resulted in generation of neurons which express dopaminergic markers TH, AADC, VMAT2 and DAT. Only neurons of GABAergic phenotype could be trans-differentiated towards a dopaminergic neurotransmitter phenotype, while for glutamatergic neurons, this process proved to be neurotoxic. Intriguingly, GABAergic neurons isolated from embryonal midbrain could not be trans-differentiated into dopaminergic neurons by Ascl1 and Nurr1. Thus, in principle, post-mitotic embryonal neurons can serve as templates for neurons with a desired neurotransmitter phenotype. However, neurotransmitter phenotype plasticity critically depends on the differentiation history of the template neurons, which can result in relatively low yields of dopaminergic neurons.

Indexed as

Cell TransdifferentiationAnimalsBasic Helix-Loop-Helix ProteinsCellular ReprogrammingCerebral CortexDopamineGABAergic NeuronsGlutamic AcidHEK293 CellsHomeodomain ProteinsHumansLIM-Homeodomain ProteinsNeurotransmitter AgentsNuclear Receptor Subfamily 4, Group A, Member 2PhenotypeRatsAscl1 protein, ratBasic Helix-Loop-Helix ProteinsDopamineGlutamic Acidhomeobox protein PITX3Homeodomain ProteinsLIM-Homeodomain ProteinsNeurotransmitter AgentsNuclear Receptor Subfamily 4, Group A, Member 2Transcription FactorsAscl1DopamineNeurotransmitter phenotypeNurr1Trans-differentiation

Identifiers

PMID31317490
OpenAlexW2956449351

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Registered trials

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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.