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Immunity. 2017 Jul 18;47(1):183-198.e6. doi: 10.1016/j.immuni.2017.06.017.

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

Author information

1
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
2
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
3
Ecole Normale Supérieure, PSL Research University, Institut de Biologie de l'ENS (IBENS), INSERM, U1024, CNRS, UMR8197, F-75005 Paris, France.
4
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore 138648, Singapore.
5
School of Medicine, Koç University, Istanbul 34450, Turkey.
6
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 117545, Singapore.
7
Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey.
8
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
9
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
10
Stem Cell and Developmental Biology Department, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
11
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore 138648, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
12
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore. Electronic address: florent_ginhoux@immunol.a-star.edu.sg.

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.

KEYWORDS:

IPSC; co-culture; familial Mediterranean fever; hematopoiesis; induced pluripotent stem cells; macrophages; microglia; neurons; primitive; pulmonary alveolar proteinosis; resident

Comment in

PMID:
28723550
DOI:
10.1016/j.immuni.2017.06.017
[Indexed for MEDLINE]
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