Microglia alterations in neurodegenerative diseases and their modeling with human induced pluripotent stem cell and
Angélica María Sabogal-Guáqueta1, Alejandro Marmolejo-Garza2, Vítor Passos de Pádua3
1Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, The Netherlands; Department of Biomedical Sciences of Cells & Systems, section Molecular Neurobiology, Faculty of Medical Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Neuroscience Group of Antioquia, Cellular and Molecular Neurobiology Area-School of Medicine, SIU, University of Antioquia, Medellín, Colombia.
Abstract:
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.
Insights
Microglia, the brain's immune cells, play key roles in development and disease. Studying them in advanced models like organoids offers new avenues for neurodegenerative disease therapies.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are the primary innate immune cells in the central nervous system (CNS).
- Originating from the yolk-sac, they differ from ectoderm-derived CNS cells.
- Microglia are crucial for synaptic pruning, development, and modulating inflammation in aging and disease.
Purpose of the Study:
- To review the role of microglia in human neurodegenerative diseases.
- To provide an update on current model systems for studying microglia.
- To highlight strategies for modeling microglia in neurodegeneration research.
Main Methods:
- Overview of microglia's role in neurodegeneration.
- Discussion of model systems: cell lines, iPSC-derived microglia, and 3D brain organoids.
- Emphasis on transcriptomic profiling and integration into organoid models.
Main Results:
- Microglia adopt an immune-activated state in response to CNS threats.
- Current models offer insights into microglia's function and dysfunction.
- Transcriptomic profiles of iPSC-derived microglia are key to understanding their behavior.
Conclusions:
- Studying microglia in advanced models like 3D brain organoids is crucial.
- These models provide a platform for developing novel neurodegenerative disease therapies.
- Understanding microglia's dynamic roles is essential for therapeutic development.
