Induced pluripotent stem cell-derived primitive macrophages as a cellular platform to model tissue-resident macrophage differentiation and function

Specialized tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that migrate into developing tissues and terminally differentiate in situ. 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 (iMac) can terminally differentiate into specialized macrophages using growth factors and organ-specific cues. Co-culturing murine iMac with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMac differentiated in vivo into microglia following injection into the brain, and functional alveolar macrophages after engraftment in the lung. Overall design: 24 samples, 12 iMac/iMicro, 12 BM-Mac/BM-Micro. Macrophages were analysed at 4 time points (day 0, 3, 6, 12), with 3 independent replicates for each time point. Non-cocultured samples from the same batch (Day 0 iMac/BM-Mac) were used as controls for the experiment.

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Takata K, Kozaki T, Lee CZW, Thion MS, Otsuka M, Lim S, Utami KH, Fidan K, Park DS, Malleret B, Chakarov S, See P, Low D, Low G, Garcia-Miralles M, Zeng R, Zhang J, Goh CC, Gul A, Hubert S, Lee B, Chen J, Low I, Shadan NB, Lum J, Wei TS, Mok E, Kawanishi S, Kitamura Y, Larbi A, Poidinger M, Renia L, Ng LG, Wolf Y, Jung S, Önder T, Newell E, Huber T, Ashihara E, Garel S, Pouladi MA, Ginhoux F