ArticleCell stem cell2021
Activation of HERV-K(HML-2) disrupts cortical patterning and neuronal differentiation by increasing NTRK3.
Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
What it found
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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.
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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.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease.Nature reviews. Molecular cell biology · 2025Review
- Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.Vaccines · 2025Review
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- Sustained Epigenetic Reactivation in Fragile X Neurons with an RNA-Binding Small Molecule.Genes · 2025Article
- HERV-K10 as a mediator of immune modulation in hepatitis infections.Frontiers in immunology · 2025Article
- HERVs Endophenotype in Autism Spectrum Disorder: Human Endogenous Retroviruses, Specific Immunoreactivity, and Disease Association in Different Family Members.Microorganisms · 2024Review
- Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development.Nature communications · 2024Article
- Wybutosine hypomodification of tRNAphe activates HERVK and impairs neuronal differentiation.iScience · 2024Article
- Antiretroviral Drug Repositioning for Glioblastoma.Cancers · 2024Article
- Activation of human endogenous retroviruses and its physiological consequences.Nature reviews. Molecular cell biology · 2024Review
- CRISPR-TE: a web-based tool to generate single guide RNAs targeting transposable elements.Mobile DNA · 2024Article
- The evaluation of human endogenous retroviral env expression in normal and cancerous tissues of the breast.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2024Article
- Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma.The Journal of clinical investigation · 2023Article
- Retrotransposon: a versatile player in human preimplantation development and health.Life medicine · 2023Article
- The Evaluation of HERV-K np9, rec, gag Expression in Isolated Human Peripheral Blood Mononuclear Cell (PBMC) of Gastric and Colon Cancer.Advanced biomedical research · 2023Article
- The Role of HERV-K in Cancer Stemness.Viruses · 2022Review
- Influenza A Virus Infection Reactivates Human Endogenous Retroviruses Associated with Modulation of Antiviral Immunity.Viruses · 2022Article
- Role of Transposable Elements in Genome Stability: Implications for Health and Disease.International journal of molecular sciences · 2022Review
- Roles of transposable elements in the regulation of mammalian transcription.Nature reviews. Molecular cell biology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
The biological function and disease association of human endogenous retroviruses (HERVs) are largely elusive. HERV-K(HML-2) has been associated with neurotoxicity, but there is no clear understanding of its role or mechanistic basis. We addressed the physiological functions of HERV-K(HML-2) in neuronal differentiation using CRISPR engineering to activate or repress its expression levels in a human-pluripotent-stem-cell-based system. We found that elevated HERV-K(HML-2) transcription is detrimental for the development and function of cortical neurons. These effects are cell-type-specific, as dopaminergic neurons are unaffected. Moreover, high HERV-K(HML-2) transcription alters cortical layer formation in forebrain organoids. HERV-K(HML-2) transcriptional activation leads to hyperactivation of NTRK3 expression and other neurodegeneration-related genes. Direct activation of NTRK3 phenotypically resembles HERV-K(HML-2) induction, and reducing NTRK3 levels in context of HERV-K(HML-2) induction restores cortical neuron differentiation. Hence, these findings unravel a cell-type-specific role for HERV-K(HML-2) in cortical neuron development.
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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.