Evidence map›Paper›PMID 38416640›Full record

ArticleCell reports2024

Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment.

Jason W Adams, Annabelle Vinokur, Janaína S de Souza, Charles Austria, Bruno S Guerra, Roberto H Herai, Karl J Wahlin, Alysson R Muotri

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in 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
3.3field-weighted citation impact, top 9% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Novel CDKL5 targets identified in human iPSC-derived neurons.Cellular and molecular life sciences : CMLS · 2024
    Article
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

8 authors at 2 institutions in 2 countries.

Jason W AdamsDepartment of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA; Center for Academic Research and Training in Anthropogeny, University of California, San Diego, La Jolla, CA 92093, USA.
Annabelle VinokurDepartment of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.
Janaína S de SouzaDepartment of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.
Charles AustriaDepartment of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.
Bruno S GuerraDepartment of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Experimental Multiuser Laboratory, Pontifícia Universidade Católica do Paraná, Curitiba, PR 80215-901, Brazil.
Roberto H HeraiDepartment of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Experimental Multiuser Laboratory, Pontifícia Universidade Católica do Paraná, Curitiba, PR 80215-901, Brazil.
Karl J WahlinShiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA.
Alysson R MuotriDepartment of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Center for Academic Research and Training in Anthropogeny, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: muotri@ucsd.edu.
University of California San Diego · USPontifícia Universidade Católica do Paraná · BR

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Single-cell approaches to deconvolution of disease-associated signalsU19MH107367 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YEO, EUGENE WEI-MING · 2015 to 2019
$15.0M
Proteogenetics of Autism Spectrum DisordersR01MH100175 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI MUOTRI, ALYSSON R., YATES III, JOHN R · 2013 to 2025
$7.4M
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
Novel SETD5-based Molecular Mechanisms and Therapeutic Tools to Understand and Revert Neuronal Dysfunction Associated with Intellectual disability and AutismR01MH127077 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Alon Goren, Alysson R. Muotri · 2022 to 2026
$3.9M
Establishment of a causal link between AD and L1 retrotransposonsR01AG078959 · NIA · 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
Investigating neurodevelopmental toxicity of perfluoroalkyl acids and their derivatives in human brain organoids modelsR01ES033636 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LILIA M IAKOUCHEVA, Alysson R. Muotri · 2022 to 2026
$3.0M
Next generation massively multiplexed combinatorial genetic screensR01HG012351 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Trey Ideker, Prashant Mali · 2023 to 2026
$2.7M
Pluripotent Stem Cell Derived 3D Retinas for Studies of Early Onset Retinal DegenerationR01EY031318 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WAHLIN, KARL J · 2020 to 2024
$2.4M
Modeling autism with human pluripotent cellsDP2OD006495 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2009 to 2009
$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
NEI NIH HHS R01 EY031318NHGRI NIH HHS R01 HG012351NIA NIH HHS R01 AG078959NICHD NIH HHS R01 HD107788NICHD NIH HHS R21 HD109616NIDA NIH HHS R01 DA056908NIEHS NIH HHS R01 ES033636NIGMS NIH HHS T32 GM007198NIH HHS DP2 OD006495NIH HHS S10 OD026929NIMH NIH HHS R01 MH100175NIMH NIH HHS R01 MH123828NIMH NIH HHS R01 MH127077NIMH NIH HHS R21 MH128827NIMH NIH HHS R56 MH109587NIMH NIH HHS U19 MH107367NINDS NIH HHS R01 NS105969NINDS NIH HHS R01 NS123642
6 · The paper itself

Abstract

Individuals with Williams syndrome (WS), a neurodevelopmental disorder caused by hemizygous loss of 26-28 genes at 7q11.23, characteristically portray a hypersocial phenotype. Copy-number variations and mutations in one of these genes, GTF2I, are associated with altered sociality and are proposed to underlie hypersociality in WS. However, the contribution of GTF2I to human neurodevelopment remains poorly understood. Here, human cellular models of neurodevelopment, including neural progenitors, neurons, and three-dimensional cortical organoids, are differentiated from CRISPR-Cas9-edited GTF2I-knockout (GTF2I-KO) pluripotent stem cells to investigate the role of GTF2I in human neurodevelopment. GTF2I-KO progenitors exhibit increased proliferation and cell-cycle alterations. Cortical organoids and neurons demonstrate increased cell death and synaptic dysregulation, including synaptic structural dysfunction and decreased electrophysiological activity on a multielectrode array. Our findings suggest that changes in synaptic circuit integrity may be a prominent mediator of the link between alterations in GTF2I and variation in the phenotypic expression of human sociality.

Indexed as

Transcription Factors, TFIITranscription Factors, TFIIIWilliams SyndromeHumansNeuronsPhenotypeSocial BehaviorGTF2I protein, humanTranscription Factors, TFIITranscription Factors, TFIIIbrain organoidcortical organoidCP: Developmental biologyCP: NeuroscienceGTF2Ineurodevelopmentstem cellsWilliams syndrome

Identifiers

PMID38416640
PMCPMC11002531
OpenAlexW4392214362

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.