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Updated: Feb 6, 2026

Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders
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Generation and characterization of iPSC-derived microglia for in vitro modeling of stimuli-specific neuroimmune

Angela K Haskell1, Joshua A Kulas1, William E Carter1

  • 1Indiana Biosciences Research Institute, Indianapolis, Indiana, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|February 4, 2026
PubMed
Abstract

Insights

Researchers developed a human induced pluripotent stem cell (iPSC)-derived microglia (iMG) model. This model effectively mimics human microglia functions for Alzheimer's disease research and therapeutic testing.

Area of Science:

  • Neuroscience
  • Immunology
  • Stem Cell Biology

Background:

  • Microglia, the brain's immune cells, are implicated in Alzheimer's disease (AD) due to their expression of AD risk genes.
  • A robust in vitro model of human microglia is crucial for studying neuroinflammation and developing AD therapeutics.

Purpose of the Study:

  • To generate and characterize a human induced pluripotent stem cell (iPSC)-derived microglia (iMG) model.
  • To validate this iMG model for neuroimmune modeling and therapeutic screening.

Main Methods:

  • Human iPSC lines were generated via episomal reprogramming.
  • Stepwise differentiation protocols were employed to derive iMG without commercial kits.
  • iMG responses to immunogenic stimuli and anti-TREM2 antibodies were characterized.

Main Results:

  • iMG expressed key microglia signature genes and exhibited dynamic morphology and transcriptional profiles.
  • iMG demonstrated rapid myelin debris phagocytosis and altered lipid homeostasis gene expression.
  • TREM2 expression in iMG increased upon IL-4 stimulation; TREM2 antibody treatment impaired phagocytosis and upregulated chemokines.

Conclusions:

  • The iPSC-derived microglia (iMG) model provides a validated system for studying human microglia.
  • This model enables the evaluation of cellular responses to various stimuli and pharmacological agents.
  • The iMG system is suitable for assessing transcriptional and functional impacts in neuroimmune research.
Keywords:
immune responseinduced pluripotent stem cellsmicrogliamyelinphagocytosistriggering receptor on myeloid cells 2

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