Modeling microglial differentiation and function in vitro using induced pluripotent stem cells

Abstract

Event Abstract Back to Event Modeling microglial differentiation and function in vitro using induced pluripotent stem cells Florent Ginhoux1* 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 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jul 2016; Published Online: 11 Aug 2016. * 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 Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Florent Ginhoux Google Florent Ginhoux Google Scholar Florent Ginhoux PubMed Florent Ginhoux Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.