Microglia differentiation from human induced pluripotent stem cells

Grace Hodgkin

Document Type

Article

Publication Date

8-9-2024

Keywords

JMG

JAX Location

In: Student Reports, Summer 2024, The Jackson Laboratory

Abstract

Microglia, constituting about 10% of brain cells, play crucial roles in CNS development and regulation. They constantly monitor for damage, prune synapses, mediate neuronal plasticity, and phagocytose dead cells and debris. Microglia exhibit significant heterogeneity and plasticity, giving them various morphologies. Over the last decade, many microglial transcripts have been identified, including disease-associated microglia (DAMs) observed in conditions like Alzheimer's (AD) and Parkinson's (PD) diseases. DAM’s effects can be both harmful .and beneficial, depending on the disease stage and age. The study of human microglia in vivo and in vitro has proven to be challenging, whereas research relying on rodent models, immortalized cell lines, and postmortem human brain tissues, often fails to replicate the progression of these complex human diseases. Human microglia, derived from yolk sac progenitor cells, can now be studied more accurately by utilizing the differentiation potential of human induced pluripotent stem cells (hiPSCs). These cells can be reprogrammed and differentiated into microglia though signaling cascades mimicking in vivo development and their identities validated through flow cytometry (FC) and immunocytochemistry (ICC). The Jackson Laboratory’s development of human microglia from hiPSCs will enable more precise studies of neurodegenerative diseases, neuronglia interactions, and potentially novel therapeutic strategies.

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