Evidence map›Paper›PMID 24904172›Full record

ArticleStem cells translational medicine2014

Proneural transcription factor Atoh1 drives highly efficient differentiation of human pluripotent stem cells into dopaminergic neurons.

Jonathan Sagal, Xiping Zhan, Jinchong Xu, Jessica Tilghman, Senthilkumar S Karuppagounder, Li Chen, Valina L Dawson, Ted M Dawson, John Laterra, Mingyao Ying

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cells translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.9field-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

27 citing papers in PubMed, 51 citations in OpenAlex.

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  18. Childhood-Onset Schizophrenia: Insights from Induced Pluripotent Stem Cells.International journal of molecular sciences · 2018
    Review
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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

10 authors at 4 institutions in 1 country.

Jonathan SagalHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Xiping ZhanHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Jinchong XuHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Jessica TilghmanHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Senthilkumar S KaruppagounderHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Li ChenHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Valina L DawsonHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Ted M DawsonHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
John LaterraHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA.
Mingyao YingHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA; Department of Physiology and Biophysics, Howard University, Washington, D.C., USA; Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neuroscience, Department of Physiology, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana, USA ying@kennedykrieger.org.
Johns Hopkins University · USJohns Hopkins Medicine · USKennedy Krieger Institute · USHoward University · US

Funding

Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8M
Brain Cancer Stem Cell Reprogramming by c-MetR01NS073611 · NINDS · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI LATERRA, JOHN J · 2012 to 2016
$1.8M
Suppression of Glioblastoma Stem Cells by Kruppel-Like Factor 9R01NS076759 · NINDS · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI LATERRA, JOHN J · 2011 to 2015
$1.6M
NINDS NIH HHS P50 NS038377NINDS NIH HHS R01 NS073611NINDS NIH HHS R01NS073611NINDS NIH HHS R01NS076759
6 · The paper itself

Abstract

Human pluripotent stem cells (PSCs) are a promising cell resource for various applications in regenerative medicine. Highly efficient approaches that differentiate human PSCs into functional lineage-specific neurons are critical for modeling neurological disorders and testing potential therapies. Proneural transcription factors are crucial drivers of neuron development and hold promise for driving highly efficient neuronal conversion in PSCs. Here, we study the functions of proneural transcription factor Atoh1 in the neuronal differentiation of PSCs. We show that Atoh1 is induced during the neuronal conversion of PSCs and that ectopic Atoh1 expression is sufficient to drive PSCs into neurons with high efficiency. Atoh1 induction, in combination with cell extrinsic factors, differentiates PSCs into functional dopaminergic (DA) neurons with >80% purity. Atoh1-induced DA neurons recapitulate key biochemical and electrophysiological features of midbrain DA neurons, the degeneration of which is responsible for clinical symptoms in Parkinson's disease (PD). Atoh1-induced DA neurons provide a reliable disease model for studying PD pathogenesis, such as neurotoxin-induced neurodegeneration in PD. Overall, our results determine the role of Atoh1 in regulating neuronal differentiation and neuron subtype specification of human PSCs. Our Atoh1-mediated differentiation approach will enable large-scale applications of PD patient-derived midbrain DA neurons in mechanistic studies and drug screening for both familial and sporadic PD.

Indexed as

NeurogenesisAction PotentialsBasic Helix-Loop-Helix ProteinsCell LineDopaminergic NeuronsDose-Response Relationship, DrugGene Expression Regulation, DevelopmentalHumansInduced Pluripotent Stem CellsMesencephalonNeural Stem CellsOxidopamineTime FactorsTransduction, GeneticTransfectionATOH1 protein, humanBasic Helix-Loop-Helix ProteinsOxidopamineBasic helix-loop-helix transcription factorsEmbryonic stem cellsInduced pluripotent stem cellsParkinson’s diseaseTet-On

Identifiers

PMID24904172
PMCPMC4116248
OpenAlexW2026129060

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.