Evidence map›Paper›PMID 28591653›Full record

ArticleStem cell reports2017

A Highly Efficient Human Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-culture-Specific Expression Profile and Inflammatory Response.

Walther Haenseler, Stephen N Sansom, Julian Buchrieser, Sarah E Newey, Craig S Moore, Francesca J Nicholls, Satyan Chintawar, Christian Schnell, Jack P Antel, Nicholas D Allen and 4 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 333 papers.

0numbers the graph read from it
0cells of the map it votes in
333citing papers in PubMed
20.6field-weighted citation impact, top 1% 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

333 citing papers in PubMed, 621 citations in OpenAlex.

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  5. Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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273 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

14 authors at 6 institutions in 2 countries.

Walther HaenselerSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Stephen N SansomKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7FY, UK.
Julian BuchrieserSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Sarah E NeweyDepartment of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Craig S MooreDivision of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.
Francesca J NichollsDepartment of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK.
Satyan ChintawarWeatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Christian SchnellSchool of Biosciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF10 3AT, UK.
Jack P AntelMontreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Nicholas D AllenSchool of Biosciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF10 3AT, UK.
M Zameel CaderWeatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Richard Wade-MartinsDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
William S JamesSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Sally A CowleySir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. Electronic address: sally.cowley@path.ox.ac.uk.
University of Oxford · GBCardiff University · GBMemorial University of Newfoundland · CAMontreal Neurological Institute and Hospital · CAMRC Weatherall Institute of Molecular Medicine · GBWarneford Hospital · GB

Funding

Medical Research Council G0900747Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MC_PC_16034Medical Research Council MR/L023784/1Medical Research Council MR/L023784/2Medical Research Council MR/M024962/1Medical Research Council MR/N013255/1Parkinson's UK J-0901Swiss National Science Foundation 148607Wellcome Trust
6 · The paper itself

Abstract

Microglia are increasingly implicated in brain pathology, particularly neurodegenerative disease, with many genes implicated in Alzheimer's, Parkinson's, and motor neuron disease expressed in microglia. There is, therefore, a need for authentic, efficient in vitro models to study human microglial pathological mechanisms. Microglia originate from the yolk sac as MYB-independent macrophages, migrating into the developing brain to complete differentiation. Here, we recapitulate microglial ontogeny by highly efficient differentiation of embryonic MYB-independent iPSC-derived macrophages then co-culture them with iPSC-derived cortical neurons. Co-cultures retain neuronal maturity and functionality for many weeks. Co-culture microglia express key microglia-specific markers and neurodegenerative disease-relevant genes, develop highly dynamic ramifications, and are phagocytic. Upon activation they become more ameboid, releasing multiple microglia-relevant cytokines. Importantly, co-culture microglia downregulate pathogen-response pathways, upregulate homeostatic function pathways, and promote a more anti-inflammatory and pro-remodeling cytokine response than corresponding monocultures, demonstrating that co-cultures are preferable for modeling authentic microglial physiology.

Indexed as

Cells, CulturedCoculture TechniquesCytokinesDown-Regulationfms-Like Tyrosine Kinase 3HumansMacrophagesMicrogliaModels, BiologicalNeurodegenerative DiseasesNeuronsPhagocytosisPluripotent Stem CellsProto-Oncogene Proteins c-mybTranscriptomeCytokinesFLT3 protein, humanfms-Like Tyrosine Kinase 3Proto-Oncogene Proteins c-mybAlzheimer's diseasecortical neuronshumaninduced pluripotent stem celliPSCmacrophagemicroglianeurodegenerationneuroinflammationParkinson's disease

Identifiers

PMID28591653
PMCPMC5470330
OpenAlexW2623352127

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.