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Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

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.

journal_name

Immunity

journal_title

Immunity

authors

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

doi

10.1016/j.immuni.2017.06.017

subject

Has Abstract

pub_date

2017-07-18 00:00:00

pages

183-198.e6

issue

1

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(17)30277-7

journal_volume

47

pub_type

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