Modeling microglial differentiation and function in vitro using induced pluripotent stem cells
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1
Agency for Science, Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Singapore
Microglia, the resident macrophages of the central nervous system (CNS), play important roles in both CNS homeostasis and inflammation. Dysregulated microglial activity is involved in the pathogenesis of neurodegenerative disorders and neuroinflammatory diseases, rendering modulation of microglial responses an attractive therapeutic target. However, a lack of relevant microglial cell model systems has so far precluded progress toward a comprehensive characterization of microglial activation states and the mechanisms by which these states may be modulated to decelerate neurodegeneration. We have previously shown that microglia arise very early during development from primitive yolk sac (YS) macrophages. Using this concept of microglial origin, we develop methods to derive YS primitive like macrophages from murine embryonic stem cells (ESC) and human induced pluripotent stem cells (iPSC), as in vitro ESC/ iPSC differentiation towards hematopoiesis was shown to recapitulate YS primitive hematopoiesis in vivo. Using our “in house” xeno/serum-free differentiation protocol, we are able to generate primitive-like macrophages that are genetically and phenotypically similar to in vivo YS macrophages and microglia progenitors. We have also been establishing methods for the co-culture of iPSC-derived primitive macrophages with neurons derived from the same mouse iPSC batch and show that iPSC-derived macrophages efficiently differentiate into microglial cells compared to monocytes or bone marrow derived macrophages. Such co-culture model will provide insights into the mechanisms of microglia differentiation, and the interactions of microglia and neurons in both physiological and pathological neuroinflammatory conditions. Furthermore, such co-culture model has the potential to serve as an in vitro drug screening system for the development of novel therapies against brain diseases. Taken together, iPSC-derived primitive macrophages could be a useful microglial source for biological, pathophysiological, and therapeutic studies.
Keywords:
Induced Pluripotent Stem Cells,
Microglia,
microglial activation,
microglial differentiation,
primitive macrophages
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
Symposium 10: Microglia: Immune Cells or Brain Cells?
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Ginhoux
F
(2016). Modeling microglial differentiation and function in vitro using induced pluripotent stem cells.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00044
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Received:
26 Jul 2016;
Published Online:
11 Aug 2016.
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Correspondence:
Dr. Florent Ginhoux, Agency for Science, Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Singapore, Singapore, florent_ginhoux@immunol.a-star.edu.sg