4.8 Review

Advanced in vitro models: Microglia in action

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Summary: This Review discusses the ongoing efforts to generate more physiologically relevant in vitro models of Alzheimer disease, focusing on modeling AD-related changes to the blood-brain barrier, myelination, neuroinflammation, and neuronal circuits. Leveraging genomic data from patients to replicate complex brain systems using cellular reprogramming technologies, the field aims to better understand the genetic and environmental factors underlying AD.

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PAX6-positive microglia evolve locally in hiPSC-derived ocular organoids

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Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality

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A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states

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Summary: This study presents a screening platform to systematically elucidate the functional consequences of genetic perturbations in human induced pluripotent stem cell-derived microglia. The researchers identified genes controlling microglia survival, activation, and phagocytosis, as well as disease-associated genes. They also determined regulators of disease-relevant microglial states using single-cell RNA sequencing. The platform has the potential for therapeutic targeting and functional characterization of microglia.

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Summary: When brain organoids are fused with blood vessel organoids, non-neural endothelial cells and microglia are incorporated into the brain organoids.
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Construction of a 3D brain extracellular matrix model to study the interaction between microglia and T cells in co-culture

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Summary: A biomimetic 3D in vitro culture system was developed to investigate the interaction between microglia and T cells. The system allowed for enhanced invasion of T cells and activation of microglia with secretion of inflammatory cytokines. This tool provides insights into the complex cellular dynamics involved in neurodegenerative disorders.

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Summary: Brain organoids, three-dimensional neural cultures that mimic the spatiotemporal organization and function of the brain, are valuable tools for studying human brain development and diseases. Various region-specific human brain organoids have been developed to model distinct parts of the brain, offering unique opportunities for exploring regional interactions and advancing brain research. However, challenges exist in driving forward the technology and applications of brain organoids for future studies.

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Microglia and Central Nervous System-Associated Macrophages-From Origin to Disease Modulation

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Summary: The immune system of the CNS is primarily made up of specialized macrophages, which are found in both the parenchyma and CNS interfaces. These brain-resident cells are considered the most suitable targets for modulating CNS diseases, as they are plastic, long-lived, and carry a large number of risk genes for various pathologies.Recent single-cell technologies have enhanced our understanding of their molecular characteristics and functional cell states during health and perturbation.

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Regional specification and complementation with non-neuroectodermal cells in human brain organoids

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Fully defined human pluripotent stem cell-derived microglia and tri-culture system model C3 production in Alzheimer's disease

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Barcoded viral tracing of single-cell interactions in central nervous system inflammation

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