ArticleNature neuroscience2022
A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states.
Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.
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Who cites it
179 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
- Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging.The Journal of clinical investigation · 2026Review
- Translational modelling of human microglia from cultures to chimeras.Experimental & molecular medicine · 2026Review
- Metabolic reprogramming of microglia: Effects on development, disease, and therapeutic potential.Neural regeneration research · 2026Article
- Transcriptomic Signatures of Microglial Phagocytosis Reveal Diagnostic Markers and Immune Landscape in Alzheimer's Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Development and validation of a long-term co-maturation protocol for human stem cell-derived microglia and neuronal networks.Stem cell reports · 2026Article
- Recent Advances in CRISPR/Cas Technologies for Biological Discovery, Therapeutics, and Diagnostics.Biomolecules · 2026Review
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Human Stem Cell-Derived Models of the Alzheimer's Disease Neuroimmune System.International journal of molecular sciences · 2026Review
- ARID5A RNA-binding coordinates microglial defense and ferroptosis in iPSC-derived models.Nature communications · 2026Article
- Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- A massively parallel CRISPR-based screening platform for modifiers of neuronal depolarization.Nature communications · 2026Article
- Modeling stimulus-induced stress responses in microglia-like cells using a commercial iPSC-dCas9-KRAB line.Stem cell research · 2026Article
- Article
- KOLF2.1J iTF-Microglia: A standardized platform to study microglial transcriptional regulatory networks in CNS disease.iScience · 2026Article
- Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology.Biomolecules · 2026Review
- Genetic inactivation of TRPM4 does not alter the temperature-dependent movement of mouse microglia.The journal of physiological sciences : JPS · 2026Article
- CSF1R-related leukoencephalopathy: experimental models and potential for treatment.Disease models & mechanisms · 2026Review
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
- Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis.Neuron · 2026Article
119 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Microglia are emerging as key drivers of neurological diseases. However, we lack a systematic understanding of the underlying mechanisms. Here, we present a screening platform to systematically elucidate functional consequences of genetic perturbations in human induced pluripotent stem cell-derived microglia. We developed an efficient 8-day protocol for the generation of microglia-like cells based on the inducible expression of six transcription factors. We established inducible CRISPR interference and activation in this system and conducted three screens targeting the 'druggable genome'. These screens uncovered genes controlling microglia survival, activation and phagocytosis, including neurodegeneration-associated genes. A screen with single-cell RNA sequencing as the readout revealed that these microglia adopt a spectrum of states mirroring those observed in human brains and identified regulators of these states. A disease-associated state characterized by osteopontin (SPP1) expression was selectively depleted by colony-stimulating factor-1 (CSF1R) inhibition. Thus, our platform can systematically uncover regulators of microglial states, enabling their functional characterization and therapeutic targeting.
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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.