Evidence map›Paper›PMID 28416807›Full record

ArticleMolecular psychiatry2018

A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells.

N Gunhanlar, G Shpak, M van der Kroeg, L A Gouty-Colomer, S T Munshi, B Lendemeijer, M Ghazvini, C Dupont, W J G Hoogendijk, J Gribnau and 2 more

Abstract read
In one paragraph

Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing 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

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

  1. Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020
    Pooled it
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  9. Modulating alternative splicing ofScience translational medicine · 2026
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67 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.

N GunhanlarDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
G ShpakDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
M van der KroegDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
L A Gouty-ColomerDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
S T MunshiDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
B LendemeijerDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
M GhazviniDepartment of Developmental Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.
C DupontDepartment of Developmental Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.
W J G HoogendijkDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
J GribnauDepartment of Developmental Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.
F M S de VrijDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
S A KushnerDepartment of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media. This protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of 114 neurons derived from three independent iPSC lines confirmed their electrophysiological maturity, including resting membrane potential (-58.2±1.0 mV), capacitance (49.1±2.9 pF), action potential (AP) threshold (-50.9±0.5 mV) and AP amplitude (66.5±1.3 mV). Nearly 100% of neurons were capable of firing APs, of which 79% had sustained trains of mature APs with minimal accommodation (peak AP frequency: 11.9±0.5 Hz) and 74% exhibited spontaneous synaptic activity (amplitude, 16.03±0.82 pA; frequency, 1.09±0.17 Hz). We expect this protocol to be of broad applicability for implementing iPSC-based neuronal network models of neuropsychiatric disorders.

Indexed as

Action PotentialsAstrocytesCell Culture TechniquesCell DifferentiationCells, CulturedCoculture TechniquesHumansInduced Pluripotent Stem CellsNeural Networks, ComputerNeural Stem CellsNeurogenesisNeuronsPatch-Clamp Techniques

Identifiers

PMID28416807
PMCPMC5984104

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.