Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function Takata, Kazuyuki et al. Immunity, Volume 47, Issue 1, 183 - 198.e6
Abstract:
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.
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Funding Info:
This work was supported by core grants of the Singapore Immunology Network and National Research Foundation Singapore (NRF-NRFI2017-02) to F.G.; by the Strategic Positioning Fund for Genetic Orphan Diseases (SPF2012/005) and a Joint Council Office Project grant (1431AFG122) from A*STAR, Singapore to M.A.P.; by the Singapore National Medical Research Council (NMRC/CBRG/0047/2013) and an A*STAR Singapore Young Investigator Grant (BMRC YIG grant number: 13/1/16/YA/009) to B.M; and by an ERC Consolidator Grant ‘‘NImO’’ (grant number: 616080) to S.G.
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The full paper is available for download at the publisher's URL: https://doi.org/10.1016/j.immuni.2017.06.017