Evidence map›Paper›PMID 28803918›Full record

ArticleCell stem cell2017

Modeling of TREX1-Dependent Autoimmune Disease using Human Stem Cells Highlights L1 Accumulation as a Source of Neuroinflammation.

Charles A Thomas, Leon Tejwani, Cleber A Trujillo, Priscilla D Negraes, Roberto H Herai, Pinar Mesci, Angela Macia, Yanick J Crow, Alysson R Muotri

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

Article in Cell stem cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
211citing papers in PubMed, 2 pooled it
13.1field-weighted citation impact, top 1% 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

211 citing papers in PubMed, 2 syntheses or guidelines pooled it, 336 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Review
  7. LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026
    Review
  8. Review
  9. Article
  10. Review
  11. Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
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  20. Article

151 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 4 countries.

Charles A ThomasDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA.
Leon TejwaniDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA.
Cleber A TrujilloDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA.
Priscilla D NegraesDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA.
Roberto H HeraiDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA; School of Medicine, Graduate Program in Health Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
Pinar MesciDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA.
Angela MaciaDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA.
Yanick J CrowINSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Paris Descartes - Sorbonne Paris Cité University, Institut Imagine, Hôpital Necker, Paris, France; Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Alysson R MuotriDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Cellular & Molecular Medicine, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, La Jolla, CA, USA. Electronic address: muotri@ucsd.edu.
University of California, San Diego · USRady Children's Hospital-San Diego · USUniversité Paris Cité · FR

Funding

Single-cell approaches to deconvolution of disease-associated signalsU19MH107367 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HALPAIN, SHELLEY L · 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
Integrative functional genomic study of pathways impacted by recurrent autism CNVR01MH108528 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.6M
Evaluating the effect of splicing mutations on isoform networks in autismR01MH109885 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.5M
Modeling autism with human pluripotent cellsDP2OD006495 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2009 to 2009
$2.3M
The Impact of L1retrotransposition in the nervous systemR01MH094753 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2011 to 2015
$1.9M
A chimeric brain model to study human neurological diseasesR21MH107771 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2015 to 2016
$426k
A human neurodevelopmental model for Williams syndromeR56MH109587 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R., SEMENDEFERI, KATERINA · 2016 to 2016
$376k
MeCP2 regulation on LINE-1 retrotransposition in neuronsF31NS076198 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THOMAS, CHARLES A. · 2012 to 2013
$69k
European Research Council 309449Medical Research Council MR/M501803/1NIH HHS DP2 OD006495NIMH NIH HHS R01 MH094753NIMH NIH HHS R01 MH100175NIMH NIH HHS R01 MH108528NIMH NIH HHS R01 MH109885NIMH NIH HHS R21 MH107771NIMH NIH HHS R56 MH109587NIMH NIH HHS U19 MH107367NINDS NIH HHS F31 NS076198
6 · The paper itself

Abstract

Three-prime repair exonuclease 1 (TREX1) is an anti-viral enzyme that cleaves nucleic acids in the cytosol, preventing accumulation and a subsequent type I interferon-associated inflammatory response. Autoimmune diseases, including Aicardi-Goutières syndrome (AGS) and systemic lupus erythematosus, can arise when TREX1 function is compromised. AGS is a neuroinflammatory disorder with severe and persistent intellectual and physical problems. Here we generated a human AGS model that recapitulates disease-relevant phenotypes using pluripotent stem cells lacking TREX1. We observed abundant extrachromosomal DNA in TREX1-deficient neural cells, of which endogenous Long Interspersed Element-1 retrotransposons were a major source. TREX1-deficient neurons also exhibited increased apoptosis and formed three-dimensional cortical organoids of reduced size. TREX1-deficient astrocytes further contributed to the observed neurotoxicity through increased type I interferon secretion. In this model, reverse-transcriptase inhibitors rescued the neurotoxicity of AGS neurons and organoids, highlighting their potential utility in therapeutic regimens for AGS and related disorders.

Indexed as

AstrocytesAutoimmune DiseasesBase SequenceCell ExtractsChildCytosolDNAExodeoxyribonucleasesHumansInfantInfant, NewbornInflammationInterferonsLong Interspersed Nucleotide ElementsMaleMicrocephalyCell ExtractsDNAExodeoxyribonucleasesInterferonsPhosphoproteinsthree prime repair exonuclease 1Aicardi-Goutières syndromedisease modelingLINE-1neuroinflammationTREX1type I IFN

Identifiers

PMID28803918
PMCPMC5591075
OpenAlexW2745112353

What OpenQuestion holds

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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.