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Immunity ; 47(1): 183-198.e6, 2017 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-28723550

RESUMEN

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.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Hematopoyesis , Macrófagos/fisiología , Neuronas/fisiología , Células Madre Pluripotentes/fisiología , Animales , Diferenciación Celular , Células Cultivadas , Embrión de Mamíferos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neurogénesis
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