Evidence map›Paper›PMID 26503761›Full record

ArticleMolecular psychiatry2016

Generation of functional human serotonergic neurons from fibroblasts.

K C Vadodaria, J Mertens, A Paquola, C Bardy, X Li, R Jappelli, L Fung, M C Marchetto, M Hamm, M Gorris and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

82 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  6. The Therapeutic Potential of Stem Cells in Depression.International journal of molecular sciences · 2025
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22 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

12 authors.

K C VadodariaLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
J MertensLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
A PaquolaLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
C BardyLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
X LiLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
R JappelliLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
L FungLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
M C MarchettoLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
M HammThe Salk Institute for Biological Studies, La Jolla, CA, USA.
M GorrisLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
P KochInstitute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany.
F H GageLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
NCI NIH HHS P30 CA014195
6 · The paper itself

Abstract

The brain's serotonergic system centrally regulates several physiological processes and its dysfunction has been implicated in the pathophysiology of several neuropsychiatric disorders. While in the past our understanding of serotonergic neurotransmission has come mainly from mouse models, the development of pluripotent stem cell and induced fibroblast-to-neuron (iN) transdifferentiation technologies has revolutionized our ability to generate human neurons in vitro. Utilizing these techniques and a novel lentiviral reporter for serotonergic neurons, we identified and overexpressed key transcription factors to successfully generate human serotonergic neurons. We found that overexpressing the transcription factors NKX2.2, FEV, GATA2 and LMX1B in combination with ASCL1 and NGN2 directly and efficiently generated serotonergic neurons from human fibroblasts. Induced serotonergic neurons (iSNs) showed increased expression of specific serotonergic genes that are known to be expressed in raphe nuclei. iSNs displayed spontaneous action potentials, released serotonin in vitro and functionally responded to selective serotonin reuptake inhibitors (SSRIs). Here, we demonstrate the efficient generation of functional human serotonergic neurons from human fibroblasts as a novel tool for studying human serotonergic neurotransmission in health and disease.

Indexed as

AnimalsAstrocytesBasic Helix-Loop-Helix ProteinsCell LineCell TransdifferentiationCytological TechniquesDNA-Binding ProteinsFibroblastsGATA2 Transcription FactorGenetic VectorsHomeobox Protein Nkx-2.2Homeodomain ProteinsHuman Embryonic Stem CellsHumansLentivirusLIM-Homeodomain ProteinsASCL1 protein, humanBasic Helix-Loop-Helix ProteinsDNA-Binding ProteinsFEV protein, humanGATA2 protein, humanGATA2 Transcription FactorHomeobox Protein Nkx-2.2Homeodomain ProteinsLIM homeobox transcription factor 1 betaLIM-Homeodomain ProteinsNerve Tissue ProteinsNEUROG2 protein, humannkx2.2b protein, zebrafishNKX2-2 protein, humanNkx2-2 protein, mouseNuclear ProteinsTranscription FactorsZebrafish Proteins

Identifiers

PMID26503761

What OpenQuestion holds

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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.