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Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells

Dayoung Kim1, Takayuki Kondo2, Haruhisa Inoue2

  • 1Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.

Stem Cell Reports
|March 27, 2026
PubMed

Insights

Human stem cell technology allows creating human microglia-like cells. These models are crucial for understanding neurodegenerative diseases and their mechanisms.

Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Immunology

Background:

  • Neurodegenerative diseases involve progressive neuronal damage.
  • Microglia, the brain's immune cells, play a critical role in disease.
  • Genetic studies link microglial genes to neurodegenerative disease risk.

Purpose of the Study:

  • To review the development and function of microglia.
  • To discuss methods for generating human microglia-like cells from stem cells.
  • To highlight the utility of these models in studying neurodegeneration.

Main Methods:

  • Review of current literature on microglial biology and stem cell differentiation.
  • Analysis of human induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) differentiation protocols.
  • Examination of how these models recapitulate human microglial functions.

Main Results:

  • Human stem cell-derived microglia offer a relevant model for studying human microglial biology.
  • These models facilitate the investigation of disease-specific microglial phenotypes.
  • Advancements in differentiation techniques enable more accurate modeling of neurodegenerative conditions.

Conclusions:

  • Human stem cell-derived microglia are invaluable tools for neurodegeneration research.
  • These models provide insights into microglial roles in disease pathogenesis.
  • Future research can leverage these platforms to develop targeted therapies.
Keywords:
ADALSAlzheimer’s diseaseCSF1R-ALSPCSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented gliaFTDPDPSCsParkinson’s diseaseamyotrophic lateral sclerosisfrontotemporal dementiamicroglianeurodegenerative diseasesorganoidpluripotent stem cells

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