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Generation and Use of iPSC-derived Microglia to Study Neurodegenerative Diseases


Microglia play critical roles in brain development, homeostasis, and neurological disorders. Recent genetic studies have shown that polymorphisms in several microglial-enriched genes are associated with altered risk of developing Alzheimer’s disease (AD), the leading cause of age-related dementia. However, the study of human microglia has been hindered by the considerable challenges of isolating sufficient numbers of viable microglia from human brain tissue.

To address this challenge, Dr. Mathew Blurton-Jones (University of California, Irvine) and colleagues asked whether patient-derived induced pluripotent stem cells (iPSCs) could be used to produce large numbers of human microglia. Guided by prior studies of mouse microglial ontology, the group developed a two-step protocol to differentiate iPSCs first into primitive hematopoietic progenitors and then via exposure to brain-related growth factors into microglia-like cells (iMGLs).

In this webinar, Dr. Blurton-Jones will discuss the development and validation of his group's microglia differentiation approach, provide examples of the type of genetic and functional studies that can be performed using this approach, and discuss how his lab is moving forward with using iPSC-microglia to better understand the development and potential treatment of AD.

What you will learn in this webinar

  • Why iPSC-derived microglia may be useful for study Alzheimer’s disease and other brain disorders.
  • Methods for differentiating iPSCs into microglia.
  • The types of functional experiments that can be performed with iPSC-microglia.
  • The remaining challenges and promising new approaches to study microglia in vivo.

Featured Speaker

Dr. Mathew Blurton-Jones
Director
UC-Irvine Alzheimer’s Disease Research Center Induced Pluripotent Stem Cell (iPSC) Core

Dr. Blurton-Jones is an Associate Professor in the Department of Neurobiology and Behavior at the University of California, Irvine. He is also Director of the UCI Alzheimer’s Disease Research Center Induced Pluripotent Stem Cell (iPSC) Core and a member of the Sue and Bill Gross Stem Cell Research Center. Dr. Blurton-Jones received his B.A. in Biology from UC Santa Barbara and then earned his PhD in Neuroscience from UC San Diego in 2002. He then pursued postdoctoral studies in the labs of Dr. Carl Cotman and Dr. Frank LaFerla before starting his own lab in 2011 at UC Irvine. Dr. Blurton-Jones’ lab uses human induced pluripotent stem cells and transgenic animal models to examine the underlying molecular mechanisms that mediate neurodegenerative disease. His studies have shown that neural stem cells can improve cognitive and motor function in transgenic models of Alzheimer’s disease (AD) and Lewy body dementia (DLB) by elevating levels of critical neurotrophic factors and enhancing endogenous structural plasticity. His group has also provided some of the first evidence that the adaptive immune system may be able to restrain the development of AD pathology by modulating the activation state of brain-resident microglia. Most recently, his lab has developed a fully defined approach to differentiate patient-derived iPSCs into microglia and is using these cells to examine the impact of AD-associated mutations on microglial function.