Evidence map›Paper›PMID 33482100›Full record

ArticleStem cell reports2021

Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells.

Sissel Ida Schmidt, Helle Bogetofte, Louise Ritter, Jette Bach Agergaard, Ditte Hammerich, Amina Arslanagic Kabiljagic, Agnieszka Wlodarczyk, Silvia Garcia Lopez, Mia Dahl Sørensen, Mie Lærkegård Jørgensen and 6 more

Abstract read
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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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

16 authors.

Sissel Ida SchmidtDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Helle BogetofteDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Louise RitterDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Jette Bach AgergaardDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Ditte HammerichDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Amina Arslanagic KabiljagicDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Agnieszka WlodarczykDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Silvia Garcia LopezDepartment of Molecular Biology and Center of Molecular Biology Severo Ochoa, University Autonoma Madrid-C.S.I.C., Madrid, ES.
Mia Dahl SørensenDepartment of Pathology, Odense University Hospital, Odense, DK.
Mie Lærkegård JørgensenDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Justyna OkarmusDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK.
Alberto Martínez SerranoDepartment of Molecular Biology and Center of Molecular Biology Severo Ochoa, University Autonoma Madrid-C.S.I.C., Madrid, ES.
Bjarne Winther KristensenDepartment of Pathology, Odense University Hospital, Odense, DK; BRIDGE - Brain Research Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense, DK.
Kristine FreudeFaculty of Health and Medical Sciences, Department of Veterinary and Animal Sciences, Section for Pathobiological Sciences, University of Copenhagen, Copenhagen, DK.
Trevor OwensDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK; BRIDGE - Brain Research Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense, DK.
Morten MeyerDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DK; Department of Neurology, Odense University Hospital, Odense, DK; BRIDGE - Brain Research Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense, DK. Electronic address: mmeyer@health.sdu.dk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Microglia have recently been established as key regulators of brain development. However, their role in neuronal subtype specification remains largely unknown. Using three different co-culture setups, we show that microglia-secreted factors enhance dopaminergic differentiation of somatic and induced pluripotent stem cell-derived human neural stem cells (NSCs). The effect was consistent across different NSC and microglial cell lines and was independent of prior microglial activation, although restricted to microglia of embryonic origin. We provide evidence that the effect is mediated through reduced cell proliferation and decreased apoptosis and necrosis orchestrated in a sequential manner during the differentiation process. tumor necrosis factor alpha, interleukin-1β, and insulinlike growth factor 1 are identified as key mediators of the effect and shown to directly increase dopaminergic differentiation of human NSCs. These findings demonstrate a positive effect of microglia on dopaminergic neurogenesis and may provide new insights into inductive and protective factors that can stimulate in vitro derivation of dopaminergic neurons.

Indexed as

Cell DifferentiationCell ProliferationAnimalsApoptosisCell LineCells, CulturedCoculture TechniquesCytokinesDopamineDopaminergic NeuronsHumansInduced Pluripotent Stem CellsInsulin-Like Growth Factor IInterleukin-1betaMiceMice, Inbred C57BLCytokinesDopamineInsulin-Like Growth Factor IInterleukin-1betaTumor Necrosis Factor-alphaco-culturedopamineIGF1IL-1βmicroglianeuron-microglia interactionNSCsParkinson’s diseasesecretome analysisTNFα

Identifiers

PMID33482100
PMCPMC7878834

What OpenQuestion holds

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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.