ArticleNucleic acids research2021
Reactive astrocytes in ALS display diminished intron retention.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Meta-analysis of human and mouse ALS astrocytes reveals multi-omic signatures of inflammatory reactive states.Genome research · 2022Pooled it
- Intron retention in health and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- Targeting MAPK-dependent pathways to modulate reactive astrocyte pathology in neurodegeneration.Communications biology · 2026Article
- Hypoxic stress is an early pathogenic event in human VCP-mutant ALS astrocytes.Stem cell reports · 2026Article
- Intron Retention: A Reemerging Paradigm in RNA Biology and Post-Transcriptional Gene Regulation.Genes · 2025Review
- Integrated transcriptomic profiling reveals a STING-mediated Type II Interferon signature in SOD1-mutant amyotrophic lateral sclerosis models.Communications biology · 2025Article
- Review
- Review
- Study on the Polarization of Astrocytes in the Optic Nerve Head of Rats Under High Intraocular Pressure: In Vitro.Bioengineering (Basel, Switzerland) · 2025Article
- Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB.Molecular neurodegeneration · 2024Article
- Replicative aging in yeast involves dynamic intron retention patterns associated with mRNA processing/export and protein ubiquitination.Microbial cell (Graz, Austria) · 2024Article
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration.Nature reviews. Neurology · 2023Review
- Discovery of Biomarkers for Amyotrophic Lateral Sclerosis from Human Cerebrospinal Fluid Using Mass-Spectrometry-Based Proteomics.Biomedicines · 2023Article
- Towards resolution of the intron retention paradox in breast cancer.Breast cancer research : BCR · 2022Article
- The role of astrocytes in prion-like mechanisms of neurodegeneration.Brain : a journal of neurology · 2022Review
- PET imaging of reactive astrocytes in neurological disorders.European journal of nuclear medicine and molecular imaging · 2022Review
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Reactive astrocytes are implicated in amyotrophic lateral sclerosis (ALS), although the mechanisms controlling reactive transformation are unknown. We show that decreased intron retention (IR) is common to human-induced pluripotent stem cell (hiPSC)-derived astrocytes carrying ALS-causing mutations in VCP, SOD1 and C9orf72. Notably, transcripts with decreased IR and increased expression are overrepresented in reactivity processes including cell adhesion, stress response and immune activation. This was recapitulated in public-datasets for (i) hiPSC-derived astrocytes stimulated with cytokines to undergo reactive transformation and (ii) in vivo astrocytes following selective deletion of TDP-43. We also re-examined public translatome sequencing (TRAP-seq) of astrocytes from a SOD1 mouse model, which revealed that transcripts upregulated in translation significantly overlap with transcripts exhibiting decreased IR. Using nucleocytoplasmic fractionation of VCP mutant astrocytes coupled with mRNA sequencing and proteomics, we identify that decreased IR in nuclear transcripts is associated with enhanced nonsense mediated decay and increased cytoplasmic expression of transcripts and proteins regulating reactive transformation. These findings are consistent with a molecular model for reactive transformation in astrocytes whereby poised nuclear reactivity-related IR transcripts are spliced, undergo nuclear-to-cytoplasmic translocation and translation. Our study therefore provides new insights into the molecular regulation of reactive transformation in astrocytes.
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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.