Evidence map›Paper›PMID 39349966›Full record

ArticleMolecular psychiatry2025

Dysregulation of miRNA expression and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids.

Dorit Trudler, Swagata Ghatak, Michael Bula, James Parker, Maria Talantova, Melissa Luevanos, Sergio Labra, Titas Grabauskas, Sarah Moore Noveral, Mayu Teranaka and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

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

  1. Pooled it
  2. Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  10. Review
  11. Review
  12. 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

30 authors.

Dorit Trudler *Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-5835-3322
Swagata Ghatak *Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Michael Bula *Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
James ParkerNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USA.
Maria TalantovaNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Melissa LuevanosNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Sergio LabraNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-4072-1131
Titas GrabauskasNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Sarah Moore NoveralNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USA.
Mayu TeranakaNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USA.ORCID 0000-0002-4589-3370
Emily SchahrerNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Nima DolatabadiNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Clare BakkerNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Kevin LopezNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USA.
Abdullah SultanNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USA.ORCID 0000-0001-8203-4391
Parth PatelNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Agnes ChanTranslational Genomics Research Institute, Phoenix, AZ, USA.
Yongwook ChoiTranslational Genomics Research Institute, Phoenix, AZ, USA.
Riki KawaguchiDepartments of Psychiatry and Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Pawel StankiewiczDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-6456-7490
Ivan Garcia-BassetsHoward Hughes Medical Institute, School and Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Piotr KozbialHoward Hughes Medical Institute, School and Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Michael G RosenfeldHoward Hughes Medical Institute, School and Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Nobuki NakanishiNeurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USA.
Daniel H GeschwindDepartment of Neurology, Center for Autism Research and Treatment, Program in Neurobehavioral Genetics, Department of Human Genetics, Department of Psychiatry, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0003-2896-3450
Shing Fai ChanCenter for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Wei LinTranslational Genomics Research Institute, Phoenix, AZ, USA.
Nicholas J SchorkTranslational Genomics Research Institute, Phoenix, AZ, USA.
Rajesh AmbasudhanNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Stuart A LiptonNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. slipton@scripps.edu.ORCID 0000-0002-3490-1259

Funding

Novel Proteomics Approach to HIV-Associated Neurocognitive Disorder & Drug AbuseDP1DA041722 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2016 to 2020
$7.0M
Leadership in AD/ADRD Drug DiscoveryR35AG071734 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2021 to 2025
$5.4M
Omics Analyses of HIV and Substance Use DisorderR01DA048882 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI REPUNTE-CANONIGO, VEZ · 2019 to 2023
$4.3M
Dynamic Interactions of the S-Nitrosoproteome in Type 2 Diabetes/Metabolic Syndrome and Alzheimer’s DiseaseRF1AG057409 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2020
$4.1M
S-Nitrosylation-Induced Posttranslational Modification and Aberrant Cell Signaling in Sporadic Alzheimer's DiseaseR01AG056259 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2021
$3.3M
Modeling Parkinson's Disease with Isogenic hiPSC-Derived Dopaminergic NeuronsR01NS086890 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2014 to 2018
$2.1M
Viral IncRNAs Regulate Host Genomic Transcriptional Programs Associated with Sporadic Alzheimer's DiseaseR01AG074307 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MICHAEL G ROSENFELD · 2022 to 2026
$2.0M
NIA NIH HHS R01 AG056259NIA NIH HHS R01 AG074307NIA NIH HHS R35 AG071734NIA NIH HHS RF1 AG057409NIDA NIH HHS DP1 DA041722NIDA NIH HHS R01 DA048882NINDS NIH HHS R01 NS086890
6 · The paper itself

Abstract

MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic and extrasynaptic activity contributing to excitatory/inhibitory (E/I) imbalance. Notably, the predominantly extrasynaptic (e)NMDA receptor antagonist, NitroSynapsin, corrects this aberrant electrical activity associated with abnormal phenotypes. During neurodevelopment, MEF2C regulates many ASD-associated gene networks, suggesting that treatment of MHS deficits may possibly help other forms of ASD as well.

Indexed as

Autistic DisorderMEF2 Transcription FactorsMicroRNAsAutism Spectrum DisorderHaploinsufficiencyHumansInduced Pluripotent Stem CellsMutationNeurogenesisNeuronsOrganoidsMEF2C protein, humanMEF2 Transcription FactorsMicroRNAs

Identifiers

PMID39349966
PMCPMC11919750

What Socratic holds

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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 Socratic graph.