Evidence map›Paper›PMID 40541184›Full record

ArticleCell2025

Cholinergic neuronal activity promotes diffuse midline glioma growth through muscarinic signaling.

Richard Drexler, Antonia Drinnenberg, Avishai Gavish, Belgin Yalçin, Kiarash Shamardani, Abigail E Rogers, Rebecca Mancusi, Vrunda Trivedi, Kathryn R Taylor, Yoon Seok Kim and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing 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

39 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Richard DrexlerDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Antonia DrinnenbergDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Avishai GavishDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA.
Belgin YalçinDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Kiarash ShamardaniDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Abigail E RogersDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Rebecca MancusiDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Vrunda TrivediDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Kathryn R TaylorDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Yoon Seok KimDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Pamelyn J WooDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Neeraj SoniDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Minhui SuDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Alexandre RavelDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Eva TatlockDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Alexandra MidlerDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Samuel H WuDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Charu RamakrishnanDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Ritchie ChenDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Alberto E Ayala-SarmientoBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
David Rincon Fernandez PachecoBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
La'Akea SivertsAllen Institute for Brain Science, Seattle, WA, USA.
Tanya L DaigleAllen Institute for Brain Science, Seattle, WA, USA.
Bosiljka TasicAllen Institute for Brain Science, Seattle, WA, USA.
Hongkui ZengAllen Institute for Brain Science, Seattle, WA, USA.
Joshua J BreunigBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Karl DeisserothDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA. Electronic address: deissero@stanford.edu.
Michelle MonjeDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA. Electronic address: mmonje@stanford.edu.

Funding

Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KEITH LLOYD LIGON · 2013 to 2026
$33.5M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
eDyNAmiC - STANFORDOT2CA278688 · NCI · STANFORD UNIVERSITY · PI PAUL S MISCHEL · 2022 to 2026
$7.7M
Targeting the neuronal microenvironment in glioblastomaU19CA264504 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy T Batchelor · 2021 to 2026
$6.4M
Glioma Circuitry: Bridging Systems Neuroscience and CancerDP1NS111132 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2018 to 2022
$5.7M
Developing Safe and Effective GD2-CAR T Cell Therapy for Diffuse Midline GliomasR01CA263500 · NCI · STANFORD UNIVERSITY · PI MACKALL, CRYSTAL, MONJE-DEISSEROTH, MICHELLE · 2021 to 2025
$3.3M
Neuronal Regulation of Low-Grade GliomagenesisR01CA258384 · NCI · STANFORD UNIVERSITY · PI David H Gutmann, Michelle Monje-Deisseroth · 2022 to 2026
$3.1M
Neuronal activity-regulated mechanisms of glioma growthR01NS092597 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2016 to 2021
$2.1M
GESTALT Barcoding and Single-cell Transcriptomics of Tumor Cell Evolution in Personalized Tumor ModelsR33CA236687 · NCI · CEDARS-SINAI MEDICAL CENTER · PI BREUNIG, JOSHUA JOHN · 2019 to 2021
$1.2M
NCI NIH HHS OT2 CA278688NCI NIH HHS P50 CA165962NCI NIH HHS R01 CA258384NCI NIH HHS R01 CA263500NCI NIH HHS R33 CA236687NCI NIH HHS T32 CA009302NCI NIH HHS U19 CA264504NINDS NIH HHS DP1 NS111132NINDS NIH HHS R01 NS092597
6 · The paper itself

Abstract

Glutamatergic neuronal activity promotes proliferation of both oligodendrocyte precursor cells (OPCs) and gliomas, including diffuse midline glioma (DMG). However, the role of neuromodulatory brainstem neurons projecting to midline structures where DMGs arise remains unexplored. Here, we demonstrate that midbrain cholinergic neuronal activity modulates OPC and DMG proliferation in a circuit-dependent manner. Optogenetic stimulation of the cholinergic pedunculopontine nucleus (PPN) promotes glioma growth in pons, while stimulation of the laterodorsal tegmentum nucleus (LDT) drives proliferation in thalamus. DMG-bearing mice exhibit higher acetylcholine release and increased cholinergic neuronal activity over the disease course. In co-culture, cholinergic neurons enhance DMG proliferation, and acetylcholine directly acts on DMG cells. Single-cell RNA sequencing revealed high CHRM1 and CHRM3 expression in primary DMG samples. Pharmacological or genetic blockade of M1/M3 receptors abolished cholinergic activity-driven DMG proliferation. Taken together, these findings demonstrate that midbrain cholinergic long-range projections promote activity-dependent DMG growth, mirroring a parallel proliferative effect on healthy OPCs.

Indexed as

Brain NeoplasmsCholinergic NeuronsGliomaReceptors, MuscarinicAcetylcholineAnimalsCell ProliferationFemaleHumansMaleMiceMice, Inbred C57BLPedunculopontine Tegmental NucleusReceptor, Muscarinic M1Receptor, Muscarinic M3Signal TransductionAcetylcholineReceptor, Muscarinic M1Receptor, Muscarinic M3Receptors, Muscariniccholinergic neurondiffuse midline gliomaDMGgliomalaterodorsal tegmentum nucleusLDTneuronneuronal activityneuron-gliomaoligodendrocyteoligodendrogenesisOPCpedunculopontine nucleusPPN

Identifiers

PMID40541184
PMCPMC12396346

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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.