Evidence map›Paper›PMID 42452972›Full record

ArticleGlia2026

Navigating Human Astrocyte Differentiation: Direct and Rapid One-Step Differentiation of Induced Pluripotent Stem Cells to Functional Astrocytes Supporting Neuronal Network Development.

Imke M E Schuurmans, Annika Mordelt, Marta Guevara-Ferrer, Katrin Linda, Denise Duineveld, Sofia Puvogel, Marina P Hommersom, Nicky Scheefhals, Lisa Rahm, Emma Dyke and 30 more

Abstract read
In one paragraph

Article in Glia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

40 authors.

Imke M E SchuurmansDepartment of Pediatrics, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, the Netherlands.ORCID 0000-0001-6294-9471
Annika MordeltDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Marta Guevara-FerrerDevelopmental, Stem Cell and Cancer Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Katrin LindaDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Denise DuineveldDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Sofia PuvogelDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Marina P HommersomDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0002-3238-9693
Nicky ScheefhalsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Lisa RahmDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Emma DykeDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Gijs-Jan ScholtenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Caroline KnorzDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Carlos Gonzalez JimenezDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Noelle van EgmondDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Astrid OudakkerDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Chantal Bijnagte-SchoenmakerDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Hans van BokhovenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Wei WeiDevelopmental, Stem Cell and Cancer Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Samuel HofmannMedical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.
Sabine Jung-KlawitterMedical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.ORCID 0000-0001-8851-672X
Sandra Mojica-PerezDepartment of Neurology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Jack ParentDepartment of Neurology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Lidia CarotenutoVIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
Sarah WeckhuysenVIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
Nadine MaasDepartment of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands.
Ype ElgersmaDepartment of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands.
Eline van de VenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Dirk LefeberDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Anita LygeroudiDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Helga E de VriesDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Luc JordiDepartment of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
Magdalini PolymenidouDepartment of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
Teresa Mitchell-GarciaDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.
Iulia DraganDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.
Amalia DolgaDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.
Lot D de WitteDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Clara D M van KarnebeekVrije Universiteit Amsterdam, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands.
James EllisDevelopmental, Stem Cell and Cancer Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Alejandro GarantoDepartment of Pediatrics, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, the Netherlands.
Nael Nadif KasriDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0002-7448-9289

Funding

EJPRD 825575Radboud Institute for Molecular Life SciencesSickKids Restracomp FellowshipStem Cell Network Impact Grant
6 · The paper itself

Abstract

Astrocytes play a pivotal role in neuronal network development. Despite the well-known role of astrocytes in the pathophysiology of neurologic disorders, the utilization of induced pluripotent stem cell (iPSC)-derived astrocytes in neuronal networks remains limited. Here, we present a streamlined one-step protocol for the differentiation of iPSCs directly into functional astrocytes without the need for ectopic gene expression or neural progenitor cell generation. We found that culturing iPSCs directly in commercial astrocyte medium, was sufficient to differentiate iPSCs into functional astrocytes within 5 weeks. More than 60 iPSC lines were successfully differentiated into astrocytes by independent researchers across 10 independent laboratories. Validation of the iPSC-astrocyte cultures demonstrated consistent astrocyte differentiation with minimal batch-to-batch variability. In dept. characterization of a subset of iPSC lines confirmed astrocyte identity and functionality of the iPSC-astrocyte monocultures by immunofluorescence, flow cytometry, RNA sequencing, glutamate uptake assays and calcium signaling recordings. Optimization of the protocol enabled co-culture of iPSC-astrocytes with Ngn2 iPSC-derived neurons (iNeurons), promoting neuronal differentiation and synapse formation. Lastly, we used single-cell electrophysiology and multi-electrode arrays, by four independent researchers, to confirm robust neuronal network development in 5-week-old iPSC-astrocyte and iNeuron co-cultures. This protocol offers a rapid and efficient method to establish all-human astrocyte-neuron co-cultures, facilitating the investigation of cell-type-specific contributions to disease pathogenesis. Its validation across numerous iPSC lines in 10 independent laboratories highlights the reproducibility of the protocol and positions it as a platform for advancing disease modeling in human neural networks.

Indexed as

AstrocytesCell DifferentiationInduced Pluripotent Stem CellsNerve NetNeuronsCells, CulturedCoculture TechniquesHumansNeurodevelopmentastrocytesdifferentiation protocolhuman modelsiPSCsneurons

Identifiers

PMID42452972
PMCPMC13370147

What OpenQuestion holds

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LicenceCC BY-NC
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.