Microglia alterations in neurodegenerative diseases and their modeling with human induced pluripotent stem cell and other platforms

• Published in: Progress in neurobiology Vol. 190; p. 101805
• Main Authors: Sabogal-Guáqueta, Angélica María, Marmolejo-Garza, Alejandro, de Pádua, Vítor Passos, Eggen, Bart, Boddeke, Erik, Dolga, Amalia M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2020
• Subjects: iPSC; Microglia; Neurodegenerative diseases; Organoids; Transcriptomics; Neurodegenerative diseases; Organoids; Transcriptomics; iPSC; Microglia
• ISSN: 0301-0082; 1873-5118
• DOI: 10.1016/j.pneurobio.2020.101805

•Microglia have pathologic implications justifying their study in neurodegeneration.•Microglia modeling is a growing field with technical culprits to be overcome.•Generating human microglia paved the way for species-specific preclinical research.•iPSC-derived microglia resemble human microglia in their transcriptomic profile.•Microglia integrated into 3D models allows studies with other CNS-resident cells.
Microglia are the main innate immune cells of the central nervous system (CNS). Unlike neurons and glial cells, which derive from ectoderm, microglia migrate early during embryo development from the yolk-sac, a mesodermal-derived structure. Microglia regulate synaptic pruning during development and induce or modulate inflammation during aging and chronic diseases. Microglia are sensitive to brain injuries and threats, altering their phenotype and function to adopt a so-called immune-activated state in response to any perceived threat to the CNS integrity. Here, we present a short overview on the role of microglia in human neurodegenerative diseases and provide an update on the current model systems to study microglia, including cell lines, iPSC-derived microglia with an emphasis in their transcriptomic profile and integration into 3D brain organoids. We present various strategies to model and study their role in neurodegeneration providing a relevant platform for the development of novel and more effective therapies.