Immunity
Volume 47, Issue 1, 18 July 2017, Pages 183-198.e6
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Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function

https://doi.org/10.1016/j.immuni.2017.06.017Get rights and content
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Highlights

  • Human and mouse iPSCs can recapitulate YS hematopoiesis

  • Human and mouse iPSCs can differentiate into YS macrophage-like cells (iMacs)

  • iMacs can further differentiate to tissue macrophage-like cells with organ-specific cues

  • iMacs derived from an FMF patient’s iPSCs exhibit disease-specific characteristics

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.

Keywords

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

Cited by (0)

11

These authors equally contributed to the work

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These authors equally contributed to the work

13

Present address: Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan

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