ArticleMolecular psychiatry2025
CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning.
Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Immune and Autoimmune Mechanisms in Autism Spectrum Disorder: Linking Molecular Pathways to Neuropsychological Trajectories Across the Lifespan.International journal of molecular sciences · 2026Review
- CRISPR-Enabled functional genomics in hPSCs-derived neural models for autism spectrum disorder.Metabolic brain disease · 2026Review
- Systematic CRISPRi perturbation of 1,408 autism risk genes maps multilevel transcriptional convergence in human cortical neurons.bioRxiv : the preprint server for biology · 2026Article
- Review
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- Article
- A Developmental Neuroimmune Cascade Model of Autism Spectrum Disorder.International journal of molecular sciences · 2026Review
- Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo.Nature neuroscience · 2026Article
- ADNP regulates chromatin architecture and lineage fidelity during neural differentiation.PLoS genetics · 2026Article
- Review
- Mesenchymal stem/stromal cell-based therapies for autism spectrum disorder: emerging evidence and clinical prospects.Journal of translational medicine · 2026Review
- Genetic and Cortical Cell-Type Liability Architecture of Autism.Research square · 2026Article
- Ultrarare Variants in DNA Damage Repair and Mitochondrial Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome and Acute Behavioral Regression in Neurodevelopmental Disorders.Developmental neuroscience · 2026Article
- Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.Frontiers in immunology · 2026Review
- A vicious cycle of microglial dysfunction: bridging synaptic pruning and neuroinflammation across the neurodevelopmental continuum.Frontiers in immunology · 2026Review
- Epigenetic Regulation of Imprinted Genes in the Neurodevelopment of Offspring Born to Women with Preeclampsia: A Review.International journal of women's health · 2026Review
- Regulators of interferon-responsive microglia uncovered by Genome-wide CRISPRi screening.NPJ dementia · 2026Article
- Microglia in autism spectrum disorder: heterogeneity, immunometabolism, and synapse-related pathways.Frontiers in immunology · 2026Review
- Genetic and Cortical Cell-Type Liability Architecture of Autism.bioRxiv : the preprint server for biology · 2025Article
- Article
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14 authors.
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Abstract
Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification of ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations into how ASD-risk genes alter development. Most functional genomics studies have focused on the role of these genes in neurons and neural progenitor cells. However, roles for ASD risk genes in other cell types are largely uncharacterized. There is evidence from postmortem tissue that microglia, the resident immune cells of the brain, appear activated in ASD. Here, we used CRISPRi-based functional genomics to systematically assess the impact of ASD risk gene knockdown on microglia activation and phagocytosis. We developed an iPSC-derived microglia-neuron coculture system and high-throughput flow cytometry readout for synaptic pruning to enable parallel CRISPRi-based screening of phagocytosis of beads, synaptosomes, and synaptic pruning. Our screen identified ADNP, a high-confidence ASD risk genes, as a modifier of microglial synaptic pruning. We found that microglia with ADNP loss have altered endocytic trafficking, remodeled proteomes, and increased motility in coculture.
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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.