ArticleInflammation and regeneration2022
Single transcription factor efficiently leads human induced pluripotent stem cells to functional microglia.
Article in Inflammation and regeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- iPSC-Derived Microglia-like Cells Exhibit Protocol-Dependent Transcriptomic Features and Robust Phagocytosis of Glioma Cells.bioRxiv : the preprint server for biology · 2026Article
- Article
- Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.Stem cell reports · 2026Review
- Microglia-associated progression of multiple sclerosis: target identification and therapeutic engagement in human in vitro models.Experimental & molecular medicine · 2026Review
- A common 19 bp APOE enhancer deletion is protective against Alzheimer's disease in African Americans.Nature communications · 2026Article
- Exploring retinal microglia: development, degeneration, and iPSC-derived model systems.Brain structure & function · 2026Review
- Microglia derived from human induced pluripotent stem cells are regulated by osteopontin, an endogenous extracellular matrix protein maintaining immune homeostasis.Frontiers in neuroscience · 2026Article
- Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils.Alzheimer's research & therapy · 2025Article
- Transcription Factor-Based Differentiation of Pluripotent Stem Cells: Overcoming the Traps of Random Neuronal Fate.Biomedicines · 2025Review
- Impaired synaptosome phagocytosis in macrophages of individuals with autism spectrum disorder.Molecular psychiatry · 2025Article
- Advancing cell therapies with artificial intelligence and synthetic biology.Current opinion in biomedical engineering · 2025Article
- Decoding microglial functions in Alzheimer's disease: insights from human models.Trends in immunology · 2025Review
- Human pluripotent stem cell (hPSC)-derived microglia for the study of brain disorders. A comprehensive review of existing protocols.IBRO neuroscience reports · 2024Review
- Mutual interaction of neurons and astrocytes derived from iPSCs with APP V717L mutation developed the astrocytic phenotypes of Alzheimer's disease.Inflammation and regeneration · 2024Article
- Human stem cell-derived neurons and astrocytes to detect novel auto-reactive IgG response in immune-mediated neurological diseases.Frontiers in immunology · 2024Article
- The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures.Experimental neurology · 2023Article
- 'Off the shelf' immunotherapies: Generation and application of pluripotent stem cell-derived immune cells.Cell proliferation · 2023Review
- Independent prognostic biomarker FERMT3 associated with immune infiltration and immunotherapy response in glioma.Annals of medicine · 2023Article
- Asteroid impact: the potential of astrocytes to modulate human neural networks within organoids.Frontiers in neuroscience · 2023Review
- Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMicroglia are innate immune cells that are the only residential macrophages in the central nervous system. They play vital physiological roles in the adult brain and during development. Microglia are particularly in the spotlight because many genetic risk factors recently identified for neurodegenerative diseases are largely expressed in microglia. Rare polymorphisms in these risk alleles lead to abnormal activity of microglia under traumatic or disease conditions.
methodsIn the present study, to investigate the multifaceted functions of human microglia, we established a novel robust protocol to generate microglia from human induced pluripotent stem cells (hiPSCs) using a combination of cytokines and small chemicals essential for microglia ontogeny. Moreover, we highly enhanced the microglial differentiation efficiency by forcing the expression of PU.1, a crucial transcription factor for microglial development, during posterior mesoderm differentiation.
resultsBy our novel method, we demonstrated the generation of a greater number of hiPSC-derived microglia (hiMGLs, approximately 120-folds) than the prior methods (at most 40-folds). Over 90% of the hiMGLs expressed microglia-specific markers, such as CX3CR1 and IBA-1. Whole-transcriptome analysis revealed that these hiMGLs are similar to human primary microglia but differ from monocytes/macrophages. Furthermore, the specific physiological functions of microglia were confirmed through indices of lipopolysaccharide responsiveness, phagocytotic ability, and inflammasome formation. By co-culturing these hiMGLs with mouse primary neurons, we demonstrated that hiMGLs can regulate the activity and maturation of neurons.
conclusionsIn this study, our new simple, rapid, and highly efficient method for generating microglia from hiPSCs will prove useful for future investigations on microglia in both physiological and disease conditions, as well as for drug discovery.
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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.