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

Prog Neurobiol. 2020 Jul:190:101805. doi: 10.1016/j.pneurobio.2020.101805. Epub 2020 Apr 24.


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.

Keywords: Microglia; Neurodegenerative diseases; Organoids; Transcriptomics; iPSC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain* / immunology
  • Brain* / metabolism
  • Brain* / pathology
  • Humans
  • Induced Pluripotent Stem Cells*
  • Microglia* / immunology
  • Microglia* / metabolism
  • Microglia* / pathology
  • Models, Biological*
  • Neurodegenerative Diseases* / immunology
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Transcriptome*