[PDF][PDF] Induced-pluripotent-stem-cell-derived primitive macrophages provide a platform for modeling tissue-resident macrophage differentiation and function

K Takata, T Kozaki, CZW Lee, MS Thion, M Otsuka… - Immunity, 2017 - cell.com
K Takata, T Kozaki, CZW Lee, MS Thion, M Otsuka, S Lim, KH Utami, K Fidan, DS Park
Immunity, 2017cell.com
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 …
Summary
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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