ArticleMolecular psychiatry2024
TREX1 is required for microglial cholesterol homeostasis and oligodendrocyte terminal differentiation in human neural assembloids.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Engineering brain organoids: from neurodevelopmental modeling to translational barriers.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2026Review
- Stem Cell-Derived Exosomes Improve Neurological Dysfunction in a Rat Model of Moderate-to-Severe Cerebral Palsy.Stem cell reviews and reports · 2026Article
- Rigorous genetic diagnosis review in natural history studies.Orphanet journal of rare diseases · 2026Article
- Microglia-associated progression of multiple sclerosis: target identification and therapeutic engagement in human in vitro models.Experimental & molecular medicine · 2026Review
- Basic Microglial Functions and How They Go Awry in Neurodegenerative Disease.Annual review of pathology · 2026Review
- A Xeno-Free Protocol for Rapid Differentiation of Human iPSC-Derived Microglia from the KOLF2.1J Reference Line.Bioengineering (Basel, Switzerland) · 2025Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- A xeno-free protocol for rapid differentiation of human iPSC-derived microglia from the KOLF2.1J reference line.bioRxiv : the preprint server for biology · 2025Article
- Midline assembloids reveal regulators of human axon guidance.Science (New York, N.Y.) · 2025Article
- [Research progress on the cGAS-STING signaling pathway in immune-mediated inflammatory diseases in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Review
- AP-1-dependent c-Fos activation by TREX1 drives M2 macrophage polarization and mitigates osteoarthritis progression.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Atorvastatin Protects Against the Macrophage/Microglia-Related Neuroinflammation via Inhibiting Lipocalin-2 in Mouse Experimental Intracerebral Hemorrhage Model.Cellular and molecular neurobiology · 2025Article
- Petroselinic Acid from Apiaceae Family Plants Ameliorates Autoimmune Disorders Through Suppressing Cytosolic-Nucleic-Acid-Mediated Type I Interferon Signaling.Biomolecules · 2025Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Three Prime Repair Exonuclease 1 (TREX1) gene mutations have been associated with Aicardi-Goutières Syndrome (AGS) - a rare, severe pediatric autoimmune disorder that primarily affects the brain and has a poorly understood etiology. Microglia are brain-resident macrophages indispensable for brain development and implicated in multiple neuroinflammatory diseases. However, the role of TREX1 - a DNase that cleaves cytosolic nucleic acids, preventing viral- and autoimmune-related inflammatory responses - in microglia biology remains to be elucidated. Here, we leverage a model of human embryonic stem cell (hESC)-derived engineered microglia-like cells, bulk, and single-cell transcriptomics, optical and transmission electron microscopy, and three-month-old assembloids composed of microglia and oligodendrocyte-containing organoids to interrogate TREX1 functions in human microglia. Our analyses suggest that TREX1 influences cholesterol metabolism, leading to an active microglial morphology with increased phagocytosis in the absence of TREX1. Notably, regulating cholesterol metabolism with an HMG-CoA reductase inhibitor, FDA-approved atorvastatin, rescues these microglial phenotypes. Functionally, TREX1 in microglia is necessary for the transition from gliogenic intermediate progenitors known as pre-oligodendrocyte precursor cells (pre-OPCs) to precursors of the oligodendrocyte lineage known as OPCs, impairing oligodendrogenesis in favor of astrogliogenesis in human assembloids. Together, these results suggest routes for therapeutic intervention in pathologies such as AGS based on microglia-specific molecular and cellular mechanisms.
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Registered trials
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.