Evidence map›Paper›PMID 39059378›Full record

ArticleStem cell reports2024

Human microglial cells as a therapeutic target in a neurodevelopmental disease model.

Pinar Mesci, Christopher N LaRock, Jacob J Jeziorski, Hideyuki Nakashima, Natalia Chermont, Adriano Ferrasa, Roberto H Herai, Tomoka Ozaki, Aurian Saleh, Cedric E Snethlage and 6 more

Abstract read
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
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.

Pinar MesciUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA. Electronic address: pmesci@gmail.com.
Christopher N LaRockDepartment of Pediatrics, University of California San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA 92037, USA; Department of Microbiology and Immunology, Department of Medicine, Division of Infectious Diseases, Emory School of Medicine, Atlanta, GA 30322, USA.
Jacob J JeziorskiUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Hideyuki NakashimaDepartment of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Natalia ChermontUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Adriano FerrasaExperimental Multiuser Laboratory (LEM), Graduate Program in Health Sciences (PPGCS), School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná 80215-901, Brazil; Department of Informatics (DEINFO), Universidade Estadual de Ponta Grossa (UEPG), Ponta Grossa, Paraná 84030-900, Brazil.
Roberto H HeraiExperimental Multiuser Laboratory (LEM), Graduate Program in Health Sciences (PPGCS), School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná 80215-901, Brazil; Research Department, Lico Kaesemodel Institute (ILK), Curitiba, Paraná, Brazil.
Tomoka OzakiUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Aurian SalehUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Cedric E SnethlageUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Sandra SanchezUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Gabriela GoldbergUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Cleber A TrujilloUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA.
Kinichi NakashimaDepartment of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Victor NizetDepartment of Pediatrics, University of California San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA 92037, USA.
Alysson R MuotriUniversity of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037, USA; University of California, San Diego, Kavli Institute for Brain and Mind, Center for Academic Research and Training in Anthropogeny (CARTA), La Jolla, CA 92093, USA. Electronic address: muotri@ucsd.edu.

Funding

Single-cell approaches to deconvolution of disease-associated signalsU19MH107367 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2015 to 2019
$15.0M
A new brain organoid model for NeuroHIV and the impact of opioidsR01DA056908 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Alysson R. Muotri · 2022 to 2026
$3.9M
Brain pathology and function in a chronic mouse model of ZIKV transmissionR01NS105969 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MUOTRI, ALYSSON R., OLSON, STEVEN H · 2019 to 2023
$3.3M
Nextgen AD Models, Endotypes, and ScreeningRF1AG084030 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R., SUBRAMANIAM, SHANKAR · 2024 to 2024
$2.3M
The Impact of hiPSC-Derived Microglia in Human Brain Development in Health and DiseaseR01NS123642 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2021 to 2025
$2.2M
Murine 3D Engineered Tissue Model of Human MYBPC3 MutationsR01HL107367 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI RALPHE, JOHN CARTER · 2011 to 2015
$1.8M
Impact of prenatal inflammation on developing human brainR01HD107788 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Alysson R. Muotri · 2022 to 2026
$1.7M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NHLBI NIH HHS R01 HL107367NIA NIH HHS RF1 AG084030NICHD NIH HHS R01 HD107788NIDA NIH HHS R01 DA056908NIH HHS S10 OD026929NIMH NIH HHS U19 MH107367NINDS NIH HHS R01 NS105969NINDS NIH HHS R01 NS123642
6 · The paper itself

Abstract

Although microglia are macrophages of the central nervous system, their involvement is not limited to immune functions. The roles of microglia during development in humans remain poorly understood due to limited access to fetal tissue. To understand how microglia can impact human neurodevelopment, the methyl-CpG binding protein 2 (MECP2) gene was knocked out in human microglia-like cells (MGLs). Disruption of the MECP2 in MGLs led to transcriptional and functional perturbations, including impaired phagocytosis. The co-culture of healthy MGLs with MECP2-knockout (KO) neurons rescued synaptogenesis defects, suggesting a microglial role in synapse formation. A targeted drug screening identified ADH-503, a CD11b agonist, restored phagocytosis and synapse formation in spheroid-MGL co-cultures, significantly improved disease progression, and increased survival in MeCP2-null mice. These results unveil a MECP2-specific regulation of human microglial phagocytosis and identify a novel therapeutic treatment for MECP2-related conditions.

Indexed as

Methyl-CpG-Binding Protein 2MicrogliaNeurodevelopmental DisordersPhagocytosisAnimalsCoculture TechniquesDisease Models, AnimalHumansMiceMice, KnockoutNeuronsSynapsesMECP2 protein, humanMethyl-CpG-Binding Protein 2ADH-503CD11bchromatinintegriniPSCMECP2microglianeurodevelopmentneuronsphagocytosisstem cellssynaptogenesis

Identifiers

PMID39059378
PMCPMC11368698

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.